Abstract IA08: Adaptive immune dysregulation in cancer patients with SARS-CoV-2 infection

Abstract The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs, and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation, and hypercytokinemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decrease translocation of opportunistic organisms, activate mucosal immunity, and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, and safe, and economical to use.

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Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Human Immunology ◽

10.1016/j.humimm.2010.02.007 ◽

2010 ◽

Vol 71 (5) ◽

pp. 496-504 ◽

Cited By ~ 47

Author(s):

Matthew D. Morse ◽

Douglas G. McNeel

Keyword(s):

Prostate Cancer ◽

Immune Responses ◽

Cancer Patients ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Adaptive Immune Responses ◽

Adaptive Immune

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Immune Dysregulation in Cancer Patients Undergoing Immune Checkpoint Inhibitor Treatment and Potential Predictive Strategies for Future Clinical Practice

Frontiers in Oncology ◽

10.3389/fonc.2018.00080 ◽

2018 ◽

Vol 8 ◽

Cited By ~ 19

Author(s):

Ronald Anderson ◽

Bernardo L. Rapoport

Keyword(s):

Clinical Practice ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Immune Dysregulation ◽

Future Clinical Practice ◽

Inhibitor Treatment

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Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far

International Journal of Molecular Sciences ◽

10.3390/ijms22084261 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4261

Author(s):

Colm J. McElwain ◽

Fergus P. McCarthy ◽

Cathal M. McCarthy

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Immune Dysregulation ◽

Adverse Outcomes ◽

Low Grade ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Visceral Adipose ◽

Increased Susceptibility

Gestational diabetes mellitus (GDM) is an obstetric complication that affects approximately 5–10% of all pregnancies worldwide. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, and is characterized by exaggerated insulin resistance, a condition which is already pronounced in healthy pregnancies. Maternal hyperglycaemia ensues, instigating a ‘glucose stress’ response and concurrent systemic inflammation. Previous findings have proposed that both placental and visceral adipose tissue play a part in instigating and mediating this low-grade inflammatory response which involves altered infiltration, differentiation and activation of maternal innate and adaptive immune cells. The resulting maternal immune dysregulation is responsible for exacerbation of the condition and a further reduction in maternal insulin sensitivity. GDM pathology results in maternal and foetal adverse outcomes such as increased susceptibility to diabetes mellitus development and foetal neurological conditions. A clearer understanding of how these pathways originate and evolve will improve therapeutic targeting. In this review, we will explore the existing findings describing maternal immunological adaption in GDM in an attempt to highlight our current understanding of GDM-mediated immune dysregulation and identify areas where further research is required.

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Repression of interleukin-8 in the primary tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/tpk7r ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Innate Immune ◽

Interleukin 8 ◽

Immune Functions ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Adaptive Immune ◽

Antigen Presenting ◽

System 1

Cytokines are soluble factors that are critical mediators of signaling in the immune system (1). Immune control of tumor growth, is a critical component of intrinsic anti-tumor defense (2). The cytokine interleukin-8 (IL-8) functions in activation and recruitment of neutrophils, innate immune cells with respiratory burst properties that also function as antigen-presenting cells (3, 4). We found, using public and published microarray data (5, 6), that the primary tumors of breast cancer patients treated with trastuzumab (Herceptin) express markedly lower quantities of IL-8 than those not treated with trastuzumab. These data allude to potential failures of innate and adaptive immune functions of the neutrophil in patients treated with trastuzumab.

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Understanding neutropenia secondary to intrinsic or iatrogenic immune dysregulation

Hematology ◽

10.1182/hematology.2021000285 ◽

2021 ◽

Vol 2021 (1) ◽

pp. 504-513

Author(s):

Kelly Walkovich ◽

James A. Connelly

Keyword(s):

Bone Marrow ◽

Immune Response ◽

Immune Checkpoint Inhibitors ◽

Molecular Mechanisms ◽

Checkpoint Inhibitors ◽

Adaptive Immune Response ◽

Immune Dysregulation ◽

Inborn Errors ◽

T Cell Therapy ◽

Adaptive Immune

Abstract As a key member of the innate and adaptive immune response, neutrophils provide insights into the hematopoietic and inflammatory manifestations of inborn errors of immunity (IEI) and the consequences of immunotherapy. The facile recognition of IEI presenting with neutropenia provides an avenue for hematologists to facilitate early diagnosis and expedite biologically rationale care. Moreover, enhancing the understanding of the molecular mechanisms driving neutropenia in IEI—decreased bone marrow reserves, diminished egress from the bone marrow, and decreased survival—offers an opportunity to further dissect the pathophysiology driving neutropenia secondary to iatrogenic immune dysregulation, eg, immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy.

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Comprehensive Analysis of the Immune Microenvironment Reveals that CD52 is a Marker for Breast Cancer Treatment with Immune Checkpoint Inhibitors

10.21203/rs.3.rs-1078018/v1 ◽

2021 ◽

Author(s):

Qiang Wang ◽

Xuxu Liu ◽

Pengfei Wang ◽

Dankun Luo ◽

Wenqi Gao ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Adaptive Immune Response ◽

Breast Cancer Patients ◽

Immune Microenvironment ◽

Adaptive Immune

Abstract Background:Breast cancer (BC) is one of the most common tumors in women. Recent years, immune checkpoint inhibitors (ICIs) have brought good news to BC patients. Although significant achievements have been made through treatment with ICIs, some people who experience serious immune-related adverse events (IrAEs) are still insensitive to this approach. The response to ICI treatment depends on the type of tumor microenvironment (TME). Methods:WGCNA (weighted gene co-expression network analysis), ESTIMATE algorithm, LASSO regression analysis, survival analysis, functional enrichment analysis are conducted to analyze the BC data in the TCGA database. Immunohistochemistry was used to verify the expression of CD52 in BC.Results:WGCNA and ESTIMATE algorithm found that the CD52 is closely related to the immune microenvironment. CD52 highly expressed in various breast cancer subtypes, and patients with high expression of CD52 have longer survival time. Compared with the low-CD52 group, the high-CD52 group had more immune cell infiltration. TIMER database verification results showed that CD8+ T cells, activated memory CD4 T cells, memory B cells, γδ T cells, and Tregs were positively correlated with CD52 expression, while M2 macrophages were negatively correlated. CD52 can change the trend of TIC (CD8+ T) and tumor-associated macrophage (TAM) infiltration with respect to the survival time of breast cancer patients. Based on the expression of CD52, we explored the relationship between CD52 and the adaptive immune response (AIR). CD52 is a marker of AIR stratification in breast cancer patients. We constructed a CD52-related adaptive immune response gene signature (CD52rAIRGsig) which is an independent prognostic factor for breast cancer and related to genome instability and the immune cells infiltration in the TME. CD52 and CD52rAIRGsig were associated with PD-1 signaling and immune checkpoint inhibitor markers, which proves that patients with high CD52 expression and low risk of CD52rAIRGsig are more suitable for ICI treatment. We then screened chemotherapeutics for personalized medicine based on CD52rAIRGsig. Conclusion:Therefore, we have discovered a new marker to guide the treatment and prognosis of breast cancer patients with ICIs. This provides a combined treatment strategy including different combinations of ICIs combined with chemotherapeutic drugs to treat breast cancer.

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