All Articles

Sara B. Intner¹, Michelle Altrich², Niraj C. Patel¹

¹Department of Pediatrics, Levine Children’s Hospital, Atrium Health, Charlotte, NC, USA

²Viracor Eurofins, Lee’s Summit, MO, USA

Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (>1.3 𝛍g/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

Lisa M. James^1,2,3,4, Effie-Photini C. Tsilibary^1,2, Spyros Charonis^1,2, Apostolos P. Georgopoulos^1,2,3,4*

¹ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

² Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

³ Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

⁴ Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

Spyros S. Charonis ^1,2, Effie-Photini Tsilibary ^1,2, Apostolos P. Georgopoulos ^1,2*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4⁺ T cell activation by the antigen-HLA molecule complex.

Ioanna Zerva, Vasileia Pateraki, Irene Athanassakis*

Department of Biology, University of Crete, Vassilika Vouton, Heraklion 70013, Crete, Greece

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

Priya Jeyaraj

Commanding Officer, Military Dental Centre (Gough Lines), Secunderabad, Telangana, Pin- 500015, India

Introduction: Establishing an accurate diagnosis and probable prognosis of ambiguous, extensive and destructive maxillary pathologies, is imperative for an appropriate, timely and effective treatment modality to be instituted. This is particularly true in the paediatric population, in order to ensure complete elimination of the lesion, with the least possible morbidity, debility, or interference with normal jaw growth.

Objectives: To assess the diagnostic and prognostic value of Immunohistochemistry (IHC) as an adjunct to Histopathological examination (HPE), in cases of destructive paediatric maxillary pathologies. To use the information thus obtained, to select the most ideal and efficacious management protocol for each case.

Material & Methods: An extensive study was carried out on 25 cases of destructive (as evidenced clinically and radiographically) maxillary lesions, in children of ages between 5 and 16 years. Positivity for an IHC tumor marker, namely Calretinin, was employed to distinguish maxillary cysts from tumors. In addition, Labelling indices of two IHC cell proliferation markers, namely Ki-67 and PCNA, indicated the proliferative activity of constituent cells of the pathologies, which aided in predicting their aggressive nature and recurrence potential. On the basis of the above information, the choice between a conservative versus radical treatment approach was made for each individual case.

Results & Conclusion: IHC proved to be of immense value as a diagnostic marker and a prognostic indicator in the paediatric maxillary pathologies. In addition to aiding the pathologist in making an accurate confirmatory diagnosis, it also served as an invaluable tool to the surgeon, in guiding the treatment plan by indicating the likely prognosis and chances of recurrence of these lesions.

Oluwatoyin Adenike Adeyemo-Salami

Department of Biochemistry, College of Medicine, University of Ibadan, Oyo State, Nigeria

Anything that affects the absorption of nutrients and intestinal function will invariably affect the physical well-being or the health status of an individual. Cystic fibrosis is a disease condition that is autosomal recessive and affects organs that have epithelia including the gastrointestinal tract of which the intestine is part, and is the one that is primarily affected. The major aberration responsible for it is mutations in the cystic fibrosis transmembrane conductance regulator gene. Phenotypical evidence of cystic fibrosis in the intestine includes obstruction, microbial dysbiosis, inflammation, acidity in the intestinal tract, malnutrition, immune dysfunction, intestinal dysmotility, appendiceal aberrations and intussusception. All these manifestations result in maldigestion and malabsorption of lipid, protein and carbohydrate in the intestine. The effect of cystic fibrosis on the digestion of certain micronutrients was also reported.

In this review, the pathophysiology, manifestations of cystic fibrosis in the gastrointestinal tract with emphasis on the small intestine, and the effects on digestion of macronutrients and micronutrients would be discussed.

Chandreyee Datta, Ashish Bhattacharjee*

Department of Biotechnology, National Institute of Technology, Durgapur, 713209, West Bengal, India.

Corona virus disease 2019 (COVID-19), is a viral disease caused by novel corona virus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The disease was declared as a pandemic by the World Health Organisation (WHO) on March 11, 2020. Initial studies have shown the molecular resemblances in the receptor binding domains of SARS-CoV and SARS-CoV-2 which bind angiotensin converting enzyme 2 (ACE 2) receptors and helps the virus to enter into the host cells to cause infection. Illness caused by COVID19 ranges from mild common cold to life threatening acute respiratory distress syndrome (ARDS), multi-organ dysfunction and shock. The key step in converting mild disease to severe is immune dysfunction and cytokine dysregulation resulting in “cytokine storm syndrome”. Clinical investigations in patients with COVID-19 have shown that a strong upregulation of cytokine and interferon production is common feature in SARS-CoV2-induced pneumonia, with an associated cytokine storm syndrome. Consequently, spotting of existing approved therapies with proper safety profiles to treat hyperinflammation is very essential in order to reduce COVID-19 associated mortality. Till date, no specific therapeutic drugs or vaccines are available to treat COVID-19. In this review, we intended to describe how cytokine storm is associated with the severity of COVID-19 disease and also tried to find out the best possible way to manage the hyperinflammatory response due to cytokine storm during COVID-19 infection using several interleukin receptor antagonists, inhibitors, intravenous immunoglobulins, cytokine adsorption device and repurposing of pre-existing antiviral and some antimalarial drugs etc.

Nick F. Hallam¹*, Janet A. Parker²

¹Colposcopy Clinic, Women's Outpatients, Cumberland Infirmary, Carlisle, England, United Kingdom

²Manchester Cytology Centre, Division of Laboratory Medicine, Manchester University, NHS Foundation Trust, Manchester, England, United Kingdom

Malgorzata Kloc*^1,2,3, Rafik M. Ghobrial^1,2, Jacek Z Kubiak*^4,5

¹The Houston Methodist Research Institute, Houston, Texas 77030, USA

²The Houston Methodist Hospital, Department of Surgery, Houston, Texas, USA

³The University of Texas, M.D. Anderson Cancer Center, Department of Genetics, Houston Texas, USA

⁴Laboratory of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), Warsaw, Poland

⁵UnivRennes, UMR 6290, CNRS, Institute of Genetics and Development of Rennes, Cell Cycle Group, Faculty of Medicine, Rennes, France

The interferons (IFNs) are the main antiviral immune factors. Currently, various IFNs therapies are used for the treatment of human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV), cancer, and autoimmune diseases. Recently, it has been suggested that IFN-α therapy should be used to lessen the respiratory symptoms in the SARS-CoV-2 virus- infected (COVID-19) patients. The SARS-CoV-2 enters the cells by binding to the Angiotensin-converting enzyme 2 (ACE2), which by recognizing the spike S1 protein of the virus, acts as a virus receptor. Because the expression of ACE2 is induced by IFN-α, the SARS-CoV-2 virus may exploit the anti-viral response by subverting the IFN functions to further its own propagation and infectability. We discuss here how the SARS-CoV-2 may also subvert the immune response of the lung macrophages, which also express ACE2, to exacerbate the severity of the COVID-19 respiratory symptoms.

Dana Khdr Sabir¹*, Nabaz R. Khwarahm², Shakhawan M. Ali³, Hayman J Abdoul⁴, Kochar I. Mahmood⁵, Rimantas Kodzius^6,7*

¹Department of Medical Laboratory Sciences, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

²Department of Biology, College of Education, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq

³Department of Oral and Maxillofacial Surgery, School of Medicine, Faculty of Dentistry, University of Sulaimani,Sulaimani, Kurdistan Region, Iraq

⁴Department of Pharmaceutical Chemistry, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

⁵Charmo Centre for Research, Training and Consultancy, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

⁶Kaunas Technology University (KTU), 37164 Panevezys, Lithuania

⁷Ludwig Maximilian University of Munich (LMU), 80539 Munich, Germany

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is a novel strain of coronavirus that is recently identified as an etiological agent for the current pandemic respiratory illness called coronavirus disease 2019 (COVID-19). The disease might have a zoonotic origin and has infected > 19 million people around the globe with > 700,000 deaths. The published data indicate that children are generally less susceptible to contracting COVID-19. Here, we are providing a review on current hypotheses that have tried to explain the low mortality and morbidity rate among children. We believe that understanding the immunological base of children’s protection can prevent further spread of the disease.

Paola Roxana Lev^1,2, Nora Paula Goette¹, Rosana Fernanda Marta^1,2*

¹Institute of Medical Research A. Lanari, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

²Department of Hematology Research, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by the decrease in peripheral blood platelet count below 100 x 10⁹/L, and an increased bleeding risk when thrombocytopenia drops below 30 x 10⁹/L. The mechanisms leading to ITP in adults, although not completely elucidated, involves an imbalance between effector and regulatory cells that results in a breakdown of the immune tolerance. Autoantibodies are considered the main responsible for thrombocytopenia, although direct T-cell cytotoxic effect and lysis by Complement attachment and activation could also contribute to platelet elimination from circulation. In addition to increased peripheral clearance, abnormalities in platelet production also favors platelet count reduction. This review is intended to describe some specific knowledge about peripheral and bone marrow mechanisms leading to thrombocytopenia in adult ITP.

Rowland Utulu¹*, Joseph Urang³, Aishat Usman^1,2, Neni Aworabhi¹, Ugochukwu Osigwe², Muhammad Shakir Balogun^1,2, Eniola A. Bamgboye⁴

¹Nigeria Field Epidemiology and Laboratory Training Program

²African Field Epidemiology Network (AFENET), Abuja

³Rivers State Primary Healthcare Management Board, Port-Harcourt, Rivers state, Nigeria

⁴Department of epidemiology and medical statistics, faculty of public health, University of Ibadan, Nigeria

Background: WHO African region set a target for elimination of measles by 2020 and recommended member states adopt a case-based surveillance system. WHO AFRO guidelines for measles surveillance state that an optimally performing surveillance system is crucial to elimination of measles. Rivers State is one of the high burden states for measles in southern Nigeria.

Objective: This study assessed the performance of the measles case-based surveillance in Rivers state, Nigeria.

Methods: We reviewed measles case-based surveillance data in Rivers state, Nigeria from year 2011-2018.

Results: A total of 1,731 suspected cases were reported with 1,128 (65.2%) confirmed cases of measles. Majority were confirmed by epidemiologic linkage 907 (80.4%) while laboratory confirmed cases constituted 206 (18.3%). Age group 1-4 years was the most affected 443 (42.6%). For cases with vaccination status available 425 (53.1%) were unvaccinated. No discarded cases were reported from 2016 to 2018. Non-measles febrile rash illness rate target of ≥2 per 100,000 was not achieved at any point in the eight-year period. The proportion of districts/LGAs reporting >2 Non Measles-Non Rubella Febrile Rash Illness cases/year was above the minimum target of 80% in just four years.

Conclusion: The surveillance system performed poorly with sensitivity and representativeness less than optimal. Measles elimination must leverage upon existing structures for polio elimination to improve surveillance. A more detailed analysis of the system is essential to identify all the gaps that may retard elimination efforts.

Hlaing Nwe Thynn, Xiao-Feng Chen, Shan-Shan Dong, Yan Guo, Tie-Lin Yang*

Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P. R. China

Antonia I. Athanasiou*, Adamantios Athanasiou, Steven D. Spandorfer

Ronald O. Perelman and Claudia Cohen Centre for Reproductive Medicine, Weill Cornell Medicine, New York, USA

Basil Rigas¹*, Wei Huang^2,3, Robert A. Honkanen²

¹Departments of Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794-8175; USA

²Departments of Ophthalmology, Stony Brook University, Stony Brook, NY, 11794-8175; USA

³Second Xiangya Hospital, Central South University, Changsha, Hunan, CN, China

Elisa Claeys, Kurt Vermeire*

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium

Organ transplantation is a life-saving therapeutic intervention that contributes to a better quality of life in patients with end-stage organ failure. Drastically improved outcome after organ transplantation occurred with the discovery and use of immunosuppressive drugs to prevent or treat allograft rejection. Development of several immunosuppressive agents offers the option for a multidrug approach with non-overlapping toxicities. Still, the side effects of these agents can be severe, resulting in a shorter life expectancy for transplant patients compared to the general population. Therefore, the development of new immunosuppressive therapies that promote immune tolerance without the side effects observed today is needed. In this review, we will discuss the mechanism of allograft rejection as well as the mode of action and side effects of currently used immunosuppressive agents.

Abbreviations

APC, antigen-presenting cell; ATG, antithymocyte globulin; IL, interleukin; MHC, major histocompatibility complex; MMF, mycophenolate mofetil; mTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T cells; Th, T helper; Treg, regulatory T

Yongming Sang*

Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN, USA

Obesity and its related comorbidities are prevailing globally. Multiple factors are etiological to cause obesity and relevant metabolic disorders. In this regard, some pathogenic infections including those by viruses have also been associated with obesity (termed as infectobesity). In this mini-review, I examined recent publications about primary or cofactorial role of viral infections to exacerbate the local and systemic immunometabolic cues that underlie most cofactorial obesity. Major immuno-metabolic pathways involved, including that mediated by interferon (IFN) signaling and peroxisome proliferator activated receptor-γ (PPAR-γ), are discussed.

Varsha Jain¹, Sriram Venigalla¹, Kevin T. Nead¹, Wei-Ting Hwang², John N. Lukens¹, Tara C. Mitchell³, Jacob E. Shabason¹*

¹Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

²Department of Biostatistics, Epidemiology and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

³Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Pre-clinical data from animal models suggest that the anti-tumor efficacy of immune checkpoint blockade agents may be influenced by gender specific sex hormones. However, recent meta-analyses of clinical data aimed at addressing the impact of gender on response to these agents have demonstrated conflicting results. Given the discordant evidence, we sought to evaluate the association of gender with the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. This retrospective cohort study used the National Cancer Database to identify patients who were ≥18 years old with Stage IV melanoma from 2011 to 2015. Patterns of utilization of immunotherapy, including by gender, were assessed using multivariable logistic regression. A multivariable Cox proportional hazards model, including an interaction term between the receipt of immunotherapy and gender, was used to evaluate whether gender modified the association of receipt of immunotherapy with hazards of death. 11,944 patients met study inclusion criteria. Of these, 8,093 (68%) were males and 3,851 (32%) were females. 2,930 (25%) patients received immunotherapy while 9,014 (75%) did not. There was no statistically significant difference in the receipt of immunotherapy between males and females. On multivariable analysis, receipt of immunotherapy was associated with a survival benefit in both males and females. However, a statistically significant difference in efficacy of immunotherapy based on gender was not observed (p_interaction =0.422). Utilizing a real world cohort of patients derived from a national cancer registry, gender was not associated with differences in immunotherapy survival outcomes in patients with metastatic melanoma.

Bai Li, Tangxin Gao, Jing Du *

School of Medicine, Yunnan University, 2 Cuihu North Road, Kunming, 650091, Yunnan, China

Masaharu Takamori*

Neurological Center, Kanazawa-Nishi Hospital, Kanazawa, Ishikawa, 920-0025, Japan

The neuromuscular junction (NMJ) is organized by a complex architecture and various signals orchestrated by sophisticated interactions. They include the presynaptic Ca²⁺ homeostasis for acetylcholine (ACh) release in the active zone organization, the post-synaptic ACh receptor (AChR) clustering at endplate membranes, the trans-synaptic communication from muscle to nerve, and the synaptic stabilization. The present data and discussions are concerned in an adaptive change of ACh release from the nerve terminal and its immunological impairment in the post-synaptic disease (myasthenia gravis, MG) and the presynaptic disease (Lambert-Eaton myasthenic syndrome, LEMS).?Discussions mainly focus the antibody-induced failure of the synaptic compensatory mechanisms that are brought about by the presynaptic autoreceptors (the M1-type muscarinic AChR [mAChR] cooperated with adenosine receptors), and the non-voltage-gated Ca²⁺-dominant influx channel (transient receptor potential canonical [TRPCs], particularly its phenotype TRPC3). Besides the synaptic transmission fatigue, the TRPC3 antibodies are discussed in terms of their implication in the muscle contraction fatigue that often occurs in the thymoma-associated MG and reflects a defect in the physiological association of TRPC3 with the ryanodine receptor-1 in the excitation-contraction coupling in which the sarcoplasmic Ca²⁺ release takes place. In addition to the modulating role in the NMJ functions, the mAChRs participate in the innate and adaptive inmmunity by MG thymus and in the lung cancer (often associated with LEMS) growth.

Paolo Lissoni*, Giusy Messina, Franco Rovelli, Nicoletta Merli, Rosa Cusmai, Fernando Brivio, Arianna Lissoni, Giuseppe Di Fede

Institute of Biological Medicine, Milan, Italy

The future of laboratory analyses would require the identification of clinical parameters involving the main integrative biological functions including neuroendocrine, immune and cardiovascular systems, and capable of predicting the evidence of metabolic alterations and the possible occurrence of systemic diseases. According to the clinical data available up to now, the status of health may be identified by the following five major biomarkers, consisting of normal circadian rhythm of cortisol and the pineal hormone melatonin, normal blood concentrations of fatty acid amide hydrolase (FAAH), whose increase is associated with an endocannabinoid system deficiency, normal lymphocyte-to-monocyte ratio (LMR) values, normal blood levels of TGF-beta, the main immunosuppressive anti-inflammatory endogenous molecule, and normal values of ANP-to-ET-1 ratio. Since the evidence of alterations involving these five parameters may predispose to the onset of more severe metabolic disorders or systemic disease, the clinical evaluation of these five biomarkers could constitute the routinary laboratory analyses for realizing a real Preventive Medicine.

Richard White¹, Stephen Abel², Shaakir Hasan², Vivek Verma², Tulika Ranjan³, Stephen M. Karlovits², Rodney E Wegner²*

¹Allegheny Health Network, Department of Internal Medicine, Pittsburgh, PA, USA

²Allegheny Health Network Cancer Institute, Division of Radiation Oncology, Pittsburgh, PA, USA

³Allegheny Health Network Cancer Institute, Division of Neuro Oncology, Pittsburgh, PA, USA

Glioblastoma (GBM) carries an abysmal prognosis. Current standard of care involves an aggressive multimodality approach including surgical resection followed by adjuvant chemoradiation. Despite this approach, overall survival remains poor and treatment approaches continue to evolve. Given the successes of immunotherapy in other disease sites, implementation in GBM management may improve outcomes. We conducted this retrospective National Cancer Database (NCDB) study to analyze treatment trends and outcomes from 2004-2015 regarding immunotherapy for GBM and queried for patients diagnosed between 2004-2015 with GBM and excluded patients treated without surgery, extracranial radiation, or chemotherapy as well as those lost to follow up.

Of the 39,317 eligible patients in this study, 511 were treated with immunotherapy and 38,806 lack thereof. Median overall survival for all patients was 15 months with a 2 and 5 year survival rate of 29% and 8%, respectively. Factors positively influencing delivery of immunotherapy included younger age, higher income, facility location in a metropolitan location, greater distance to the treatment facility, treatment at an academic facility, treatment outside of the years 2007 to 2009, and Caucasian race. On propensity matched analysis, survival was 18 months and 17 months with and without immunotherapy, respectively (p=0.15). Higher comorbidity, lower income, and male gender predicted for worse survival.

The results of the NCDB analysis showed an initial decrease and then increase in the use of immunotherapy in the management of GBM. Propensity-matched analyses did not show an overall survival benefit.

Rodney E. Wegner¹*, Stephen Abel¹, Shaakir Hasan¹, Richard J. White¹, Gene Finley², Dulabh Monga², Athanasios Colonias¹, Vivek Verma¹

¹Allegheny Health Network Cancer Institute, Division of Radiation Oncology, USA

²Allegheny Health Network Cancer Institute, Division of Medical Oncology, USA

Immunotherapy (IMT) has revolutionized the treatment of stage IV non-small cell lung cancer (NSCLC). However, optimal timing of IMT in relation to stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) is unknown. Utilizing the National Cancer Database, we examined trends in IMT use in metastatic NSCLC patients and the potential survival implications of IMT timing in relation to SBRT/SRS. We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015. Patients receiving IMT and SBRT/SRS to any site were included. Multivariate logistic regression identified predictors of IMT use. Receiver operator characteristic curve analysis determined an a priori timeframe between SBRT and IMT predictive of optimal overall survival (OS). Univariate and multivariate analyses identified factors predictive of OS. Propensity-adjusted Cox proportional hazard ratios were used to mitigate indication bias. Of 13,862 eligible patients, 371 received IMT. The majority (75%) received chemotherapy. IMT use was associated with improved median OS on univariate analysis (17 vs. 13 months, p<0.0001). Adenocarcinoma histology, chemotherapy use, and recent treatment year were associated with IMT. On multivariate propensity-adjusted Cox regression, predictors for improved OS included: younger age, lower comorbidity score, lower grade, private insurance, IMT use, and female sex. Patients treated ≥ 21 days (a priori threshold) after SBRT/SRS initiation had improved median OS (19 vs. 15 months, p=0.0335). In patients with Stage IV NSCLC, IMT use following SBRT/SRS has increased. OS improved when IMT was given ≥3 weeks after initiating SBRT/SRS; suggesting a potential optimal time-frame between RT and IMT.

Greg A. Kirchenbaum, Jodi Hanson, Diana R. Roen, Paul V. Lehmann*

Cellular Technology Limited (CTL) Shaker Heights, OH, 44122-5350, USA

T cells not only protect us from infectious diseases and cancer, but are also involved in transplant rejection, autoimmune diseases, and allergies. Each of these immunologic processes share a common link in which antigen-specific T cells undergo expansion, with some of the resulting progeny differentiating into memory cells. Memory T cells belong to several distinct lineages, and sub-lineages, that fundamentally differ in their effector functions and capacity to mediate a protective or pathological immune response. In this mini-review, we outline how such memory T cell subpopulations can readily be identified on the basis of their secretory signature using a multi-color ImmunoSpot® assay.

Hildegard M Schuller*

Department of Biomedical & Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA

This mini-review summarizes current knowledge on similarities and synergism between smoking and psychological stress-induced modulations of growth stimulating and inhibiting regulatory networks in epithelial cells and epithelial cancers with emphasis on cancer stimulating neurotransmitters and their receptors as well as cancer inhibiting γ-aminobutyric acid (GABA) and opioids. Hyperactive cAMP signaling downstream of beta-adrenergic receptors (β-ARs) has been identified as the driving force of most smoking-associated cancers by numerous preclinical studies and psychological stress intensifies these effects while experimental stress reduction inhibits. The integration of cAMP reduction via stress reduction by pharmacological and psychological means such as psychotherapy, relaxation meditation and yoga into any cancer treatment strategy is recommended.