Role of Co-inhibitory Molecules in Tumor Escape from CTL Attack

2015 ◽  
pp. 31-58
Author(s):  
Wieger J. Norde ◽  
Willemijn Hobo ◽  
Harry Dolstra
Keyword(s):  
Tumor Escape ◽  
Inhibitory Molecules

Obesity and inflammation: colorectal cancer engines

2021 ◽  
Vol 14 ◽  
Author(s):  
Lara J. Bou Malhab ◽  
Wael M. Abdel-Rahman
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Obese Patients ◽  
Epigenetic Alterations ◽  
Molecular Alterations ◽  
Stat3 Signaling ◽  
Therapeutic Choice ◽  
Prevalence Of Obesity ◽  
Inhibitory Molecules

: The prevalence of obesity continues to increase to the extent that it became a worldwide pandemic. An accumulating body of evidence has associated obesity with the development of different types of cancer, including colorectal cancer, which is a notorious disease with a high mortality rate. At the molecular level, colorectal cancer is a heterogenous disease characterized by a myriad of genetic and epigenetic alterations associated with various forms of genomic instability (detailed in Supplementary Materials). Recently, the microenvironment has emerged as a major factor in carcinogenesis. Our aim is to define the different molecular alterations leading to the development of colorectal cancer in obese patients with a focus on the role of the microenvironment in carcinogenesis. We also highlight all existent molecules in clinical trials that target the activated pathways in obesity-associated colorectal cancer, whether used as single treatments or in combination. Obesity predisposes to colorectal cancer via creating a state of chronic inflammation with dysregulated adipokines, inflammatory mediators, and other factors such as immune cell infiltration. A unifying theme in obesity-mediated colorectal cancer is the activation of the PI3K/AKT, mTOR/MAPK, and STAT3 signaling pathways. Different inhibitory molecules towards these pathways exist, increasing the therapeutic choice of obesity-associated colon cancer. However, obese patients are more likely to suffer from chemotherapy overdosing. Preventing obesity through maintaining a healthy and active lifestyle remains to be the best remedy.

Modulation of dendritic cell and T cell cross-talk during aging: The potential role of checkpoint inhibitory molecules

2017 ◽  
Vol 38 ◽  
pp. 40-51 ◽  
Author(s):  
Joanne K. Gardner ◽  
Cyril D.S. Mamotte ◽  
Connie Jackaman ◽  
Delia J. Nelson
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cross Talk ◽  
Potential Role ◽  
Inhibitory Molecules

scholarly journals The Role of Co-Signaling Molecules in Psoriasis and Their Implications for Targeted Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Suqing Liu ◽  
Jinhua Xu ◽  
Jinfeng Wu
Keyword(s):  
T Cells ◽  
Signaling Molecules ◽  
Pathological Process ◽  
T Cell Response ◽  
Significant Progress ◽  
Broad Application ◽  
Immune Mediated ◽  
Inhibitory Molecules ◽  
Application Prospects

Psoriasis is a chronic, systemic immune-mediated inflammatory disease manifesting in the skin, joint or both. Co-signaling molecules are essential for determining the magnitude of the T cell response to the antigen. According to the function of co-signaling molecules, they can be divided into co-stimulatory molecules and co-inhibitory molecules. The role of co-signaling molecules in psoriasis is recognized, mainly including the co-stimulatory molecules CD28, CD40, OX40, CD27, DR3, LFA-1, and LFA-3 and the co-inhibitory molecules CTLA-4, PD-1, and TIM-3. They impact the pathological process of psoriasis by modulating the immune strength of T cells, regulating the production of cytokines or the differentiation of Tregs. In recent years, immunotherapies targeting co-signaling molecules have made significant progress and shown broad application prospects in psoriasis. This review aims to outline the possible role of co-signaling molecules in the pathogenesis of psoriasis and their potential application for the treatment of psoriasis.

scholarly journals The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

2020 ◽  
Vol 10 ◽  
Author(s):  
Alana Serrano Campelo de Souza ◽  
Letícia Boslooper Gonçalves ◽  
Ana Paula Lepique ◽  
Patrícia Savio de Araujo-Souza
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
Immune Escape ◽  
Nk Cell ◽  
Nutrient Deficiency ◽  
Potential Interaction ◽  
Migration And Invasion ◽  
Inhibitory Molecules ◽  
Cancer Immunotherapies

The tumor microenvironment (TME) is complex, and its composition and dynamics determine tumor fate. From tumor cells themselves, with their capacity for unlimited replication, migration, and invasion, to fibroblasts, endothelial cells, and immune cells, which can have pro and/or anti-tumor potential, interaction among these elements determines tumor progression. The understanding of molecular pathways involved in immune escape has permitted the development of cancer immunotherapies. Targeting molecules or biological processes that inhibit antitumor immune responses has allowed a significant improvement in cancer patient’s prognosis. Autophagy is a cellular process required to eliminate dysfunctional proteins and organelles, maintaining cellular homeostasis. Usually a process associated with protection against cancer, autophagy associated to cancer cells has been reported in response to hypoxia, nutrient deficiency, and oxidative stress, conditions frequently observed in the TME. Recent studies have shown a paradoxical association between autophagy and tumor immune responses. Tumor cell autophagy increases the expression of inhibitory molecules, such as PD-1 and CTLA-4, which block antitumor cytotoxic responses. Moreover, it can also directly affect antitumor immune responses by, for example, degrading NK cell-derived granzyme B and protecting tumor cells. Interestingly, the activation of autophagy on dendritic cells has the opposite effects, enhancing antigen presentation, triggering CD8+ T cells cytotoxic activity, and reducing tumor growth. Therefore, this review will focus on the most recent aspects of autophagy and tumor immune environment. We describe the dual role of autophagy in modulating tumor immune responses and discuss some aspects that must be considered to improve cancer treatment.

The role of inhibitory molecules in fracture healing

Injury ◽  
2006 ◽  
Vol 37 (1) ◽  
pp. S20-S29 ◽  
Author(s):  
Rozalia Dimitriou ◽  
Eleftherios Tsiridis ◽  
Ian Carr ◽  
Hamish Simpson ◽  
Peter V. Giannoudis
Keyword(s):  
Fracture Healing ◽  
Inhibitory Molecules

scholarly journals Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade

2016 ◽  
Author(s):  
Pornpimol Charoentong ◽  
Francesca Finotello ◽  
Mihaela Angelova ◽  
Clemens Mayer ◽  
Mirjana Efremova ◽  
...  
Keyword(s):  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Tumor Escape ◽  
Predictors Of Response ◽  
Cancer Genome Atlas ◽  
Tumor Immunogenicity ◽  
Immune Oncology ◽  
Cancer Germline

SUMMARYThe Cancer Genome Atlas revealed the genomic landscapes of common human cancers. In parallel, immunotherapy with checkpoint blockers is transforming the treatment of advanced cancers. As only a minority of the patients is responsive to checkpoint blockers, the identification of predictive markers and the mechanisms of resistance is a subject of intense research. To facilitate understanding of the tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers, and created The Cancer Immunome Atlas (http://tcia.at). Cellular characterization of the immune infiltrates revealed a role of cancer-germline antigens in spontaneous immunity and showed that tumor genotypes determine immunophenotypes and tumor escape mechanisms. Using machine learning we identified determinants of tumor immunogenicity and developed a scoring scheme for the quantification termed immunophenoscore. The immunophenoscore was superior predictor of response to anti-CTLA-4 and anti-PD-1 antibodies in two independent validation cohorts. Our findings and the developed resource may help informing cancer immunotherapy and facilitate the development of precision immune-oncology.

Association of HLA-G Haplotype Risk Model with Overall Survival In Acute Myeloid Leukemia Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2169-2169
Author(s):  
Anja Volbracht ◽  
Juergen R Novotny ◽  
Crista Ochsenfarth ◽  
Magdalena Switala ◽  
Ulrich Frey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Tumor Escape ◽  
Tumor Immune Escape ◽  
Group A ◽  
Group B ◽  
Acute Myeloid

Abstract Abstract 2169 Introduction: The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and exerts multiple immunosuppressive functions. Thus, HLA-G expression in tumor cells favors tumor immune escape and tumor progression. The HLA-G gene polymorphism is extremely restricted in comparison to the classical HLA antigens. However, specific HLA-G polymorphisms in exons 3, 4, 5, 7 and parts of the 3′UTR encode for different haplotypes/alleles. Because of the prognostic role of HLA-G in cancer, especially in B-CLL, we investigated here the role of the HLA-G haplotypes in acute myeloid leukemia (AML). Methods: Genotyping was performed on the basis of examining exons 3, 4, 5, 7 and parts of the 3′UTR by pyrosequencing in 166 patients with AML. In total, we found 17 different haplotypes in the cohort. Results: The haplotype distributions between 166 AML patients and 190 healthy controls were significantly different in two alleles, arguing that these two haplotypes of HLA-G on the one hand increases (*01:06, p=0.042) and on the other hand decreases (*01:01:12 variante, p=0.0014) the susceptibility for AML. Next a risk model was generated for overall survival (OS) adapted to specific haplotypes/alleles of the HLA-G gene. The favorable group (A) consisted of the alleles *01:06 and *01:01:20 variant at codon 57 G (12 patients), the intermediate group (B) of *01:01:20, *01:04:10, *01:01:30 and *01:01:41 variant at codon 57 A (113 patients) and the unfavorable group (C) of the remaining 11 alleles (41 patients). The OS for patients in group C was significantly (p=0.02) shorter (median OS 613 days) than for those in group B (median OS 961 days) and A (median OS not reached). Multivariate analysis shows a trend that the risk HLA-G model (Hazard ratio (HR) 1.4, p=0.084) was an independent predictor next to the established prognostic factors cytogenetics (HR 2.1, p=0.001), age (HR 1.8, p=0.009), leucocytes (HR 1.6, p=0.026), ECOG stage (HR 1.5, p=0.006) and platelets (HR 2.1, p=0.015). Moreover, the new risk model was able to further subdivide patients with intermediate cytogenetic risk profile (median OS: group A not reached; group B 987 days; group C 624 days; p=0.10). Conclusion: Our study is the first study demonstrating that the combination of different alleles of the HLA-G gene is associated with the overall survival in AML patients. This fact emphasizes the extensive role of this gene by the tumor escape mechanism and could be responsible for progress in other cancers. Disclosures: No relevant conflicts of interest to declare.

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