Capillary-leak syndrome: an unrecognized early immune adverse effect of checkpoint-inhibitors treatment

Immunotherapy ◽  
2021 ◽  
Author(s):  
Ruth Percik ◽  
Asher Nethanel ◽  
Yair Liel
Keyword(s):  
Adverse Effect ◽  
Immune Response ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Endothelial Damage ◽  
Capillary Leak Syndrome ◽  
Capillary Leak ◽  
Cytokine Activation ◽  
Complex Interactions ◽  
Cellular Immune

Capillary-leak syndrome is strongly associated with cytokine activity states. It is an ill-recognized adverse effect of checkpoint inhibitors treatment, which are typically associated with cellular immune response. We describe two patients with capillary leak syndrome following immune checkpoint inhibitors treatment. We present linking mechanisms between checkpoint inhibitors, cellular immunity, cytokine action and endothelial damage. We suggest that capillary-leak syndrome is a unique adverse effect of immunotherapy, resulting from complex interactions between cellular and cytokine activation and that its expression is probably depending on inherent host immune variabilities.

scholarly journals Immune System Efficiency in Cancer and the Microbiota Influence

Pathobiology ◽  
2021 ◽  
pp. 1-17
Author(s):  
Ana Margarida Barbosa ◽  
Alexandra Gomes-Gonçalves ◽  
António G. Castro ◽  
Egídio Torrado
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Checkpoint Inhibitors ◽  
Therapeutic Response ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
System Efficiency ◽  
Novel Targets ◽  
Cancer Immunosurveillance

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

scholarly journals Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217260
Author(s):  
Tommaso Morelli ◽  
Kohei Fujita ◽  
Gil Redelman-Sidi ◽  
Paul T Elkington
Keyword(s):  
Immune Response ◽  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Treatment ◽  
Common Side Effect ◽  
Inflammatory Immune Response ◽  
New Framework

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

scholarly journals PREDICTIVE RESPONSE MARKERS FOR IMMUNE RESPONSE BLOCKS

2020 ◽  
Vol 19 (4) ◽  
pp. 123-131
Author(s):  
G. A. Janus ◽  
A. G. Ievleva ◽  
E. N. Suspitsyn ◽  
V. I. Tyurin ◽  
I. V. Bizin ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Predictive Power ◽  
Checkpoint Inhibitors ◽  
Significant Proportion ◽  
Histocompatibility Complex ◽  
Mutation Burden ◽  
Selection Of Patients ◽  
Selection Of

Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.

scholarly journals EP1.04-44 Exploration of Factors Relating to Paradoxical Immune Response in Patients Treated with Immune Checkpoint Inhibitors for NSCLC

2019 ◽  
Vol 14 (10) ◽  
pp. S971
Author(s):  
A.F. Cardona ◽  
O.G. Arrieta ◽  
A. Ruiz-Patiño ◽  
Z.L. Zatarain Barrón ◽  
L.L. Rojas ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

SLAMF8, a novel biomarker for personalized immune checkpoint blockade therapy in gastrointestinal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14078-e14078
Author(s):  
Qun Zhang ◽  
Lei Cheng ◽  
Jing Hu ◽  
Li Li ◽  
Mi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Normal Tissues ◽  
Ebv Infection

e14078 Background: Immune checkpoint inhibitors have brought great breakthroughs in cancer therapy. Activated immune response is known to be the prerequisite for exerting immunotherapy efficacy. Epstein-Barr virus (EBV) infection is associated with longer survival in gastric cancer (GC) patients due to enhanced anti-tumor immune response, and therefore it was reportedly played an important role in modulating immune checkpoint blockade therapy efficacy. However, molecular dimensions underlying the good response to immune checkpoint inhibitors in presence of EBV infection are still unclear. The aim of this study is to identify a gene signature related to EBV induced anti-tumor immune response, and select a tag gene from this signature to predict which patients are most likely to benefit from immune checkpoint blockade therapy. Methods: Two large transcriptome datasets from Gene Expression Omnibus(GEO) database (GSE51575 and GSE62254) were used to screen gene signature for EBV infected gastric cancer tissues. We further selected genes that showed a trend towards differential co-expression independent of EBV infection status. The tag gene of this differential co-expression signature was finally identified by bioinformatics analysis. To make an external validation, we performed RNA sequencing in 20 colorectal caner (CRC) tissues and 20 GC tissues, respectively. Meanwhile, tissue microarrays of CRC cohort (36 paired tumor and normal tissues) and GC cohort (75 paired tumor and normal tissues) were used to analyze the association of SLAMF8 with CD8 protein expression by immunohistochemistry (IHC). Results: Analysis of GEO datasets indicated 788 genes as feature gene cluster for EBV-positive gastric cancer, from which 290 genes were selected to be characterized by differential co-expression in either EBV-positive or EBV-negative gastric cancers. SLAMF8 was identified as the tag gene for this differential co-expression signature. This signature, tagged by SLAMF8, was successfully validated by our RNA sequencing data in presence of its good performance in dividing CRC and GC patients into two subsets. Moreover, we observed a significant association between SLAMF8 and CD8 expression in our CRC and GC tissue samples, in terms of either mRNA or protein level. Conclusions: SLAMF8, a potential indicator for T cell‐mediated immune response induced by EBV infection, may be served as a biomarker for individualized immune checkpoint blockade therapy in gastrointestinal cancer. Further SLAMF8 guided drug sensitivity tests are warranted to validate our results.

scholarly journals The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors

2021 ◽  
Vol 15 ◽  
pp. 117955492199628
Author(s):  
Zhaozhen Wu ◽  
Pengfei Cui ◽  
Haitao Tao ◽  
Sujie Zhang ◽  
Junxun Ma ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Damage ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Resistance Mechanisms ◽  
Great Promise ◽  
Immunogenic Cell Death

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise for treating cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing tumor neoantigen, upregulation of interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different malignancies. However, only a subset of populations derive clinical benefit, and the biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen.

scholarly journals Understanding neutropenia secondary to intrinsic or iatrogenic immune dysregulation

Hematology ◽  
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.

scholarly journals Lymphopenia in Esophageal Cancer: What Have We Learned?

2021 ◽  
Vol 11 ◽  
Author(s):  
Jia-Lin Wang ◽  
Rong Ma ◽  
Wei Kong ◽  
Ren Zhao ◽  
Yan-Yang Wang
Keyword(s):  
Adverse Effect ◽  
Esophageal Cancer ◽  
Immune System ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Lymphocyte Count ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patients With Cancer ◽  
The Status

Lymphopenia caused by disease or treatment is frequent in patients with cancer, which seriously affects the prognosis of these patients. Immune checkpoint inhibitors (ICIs) have garnered attention as one of the most promising strategies for the treatment of esophageal cancer (EC). The status of the immune system, such as, the lymphocyte count, is now considered to be an important biomarker for ICI treatments. Recognition of the significant impact of the lymphocyte count on the survival of patients with EC in the era of immunotherapy has revived interest in understanding the causes of lymphopenia and in developing strategies to predict, prevent and eliminate the adverse effect of lymphopenia. Here, we review what we have learned about lymphopenia in EC, including the prognostic and predictive value of lymphopenia in patients with EC, the predictors of lymphopenia, and the strategies to ameliorate the effect of lymphopenia in patients with EC.

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