Polarization of M2 Macrophages to Promote Tumor Immune Escape via Il-10 in SCLC but Not NSCLC Patients

2019 ◽  
Author(s):  
Xintong Hu ◽  
Yue Gu ◽  
Songchen Zhao ◽  
Shucheng Hua ◽  
Yanfang Jiang
Keyword(s):  
Immune Escape ◽  
M2 Macrophages ◽  
Tumor Immune Escape ◽  
Nsclc Patients

scholarly journals Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Valentin Baloche ◽  
Julie Rivière ◽  
Thi Bao Tram Tran ◽  
Aurore Gelin ◽  
Olivia Bawa ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Immune Escape ◽  
Interferon Γ ◽  
Inflammatory Factor ◽  
Tumor Immune Escape ◽  
Bladder Carcinoma Cell Line ◽  
Consistent Change ◽  
Changing Patterns ◽  
Serial Transplantation

AbstractMechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infiltrating cells, the contribution of gal-9 produced by malignant cells has never been demonstrated in an animal model. Therefore, we derived isogenic clones—either positive or negative for gal-9—from the MB49 murine bladder carcinoma cell line. A progressive and consistent reduction of tumor growth was observed when gal-9-KO cells were subjected to serial transplantations into syngeneic mice. In contrast, tumor growth was unaffected during parallel serial transplantations into nude mice, thus linking tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. This stronger immune response was at least in part explained by changing patterns of response to interferon-γ. One consistent change was a more abundant production of CXCL10, a major inflammatory factor whose production is often induced by interferon-γ. Overall, these observations demonstrate for the first time that serial transplantation into syngeneic mice can be a valuable experimental approach for the exploration of novel mechanisms of tumor immune escape.

scholarly journals Tumor-infiltrating T-regulatory cells adapt to altered metabolism to promote tumor-immune escape

2021 ◽  
Vol 2 ◽  
pp. 132-141
Author(s):  
Tania Sarkar ◽  
Subhanki Dhar ◽  
Gaurisankar Sa
Keyword(s):  
T Regulatory Cells ◽  
Immune Escape ◽  
Regulatory Cells ◽  
Tumor Immune Escape ◽  
Altered Metabolism

Abstract 495: TNFR2 and PD-1/PD-L1/TNFR2 humanized mice aiding exploration of combination strategies to overcome tumor immune escape mechanisms

2021 ◽  
Author(s):  
Huilin Li ◽  
Xiaofei Zhou ◽  
Jing Zhang ◽  
Veronika Chromikova ◽  
Qingcong Lin
Keyword(s):  
Immune Escape ◽  
Humanized Mice ◽  
Tumor Immune Escape ◽  
Combination Strategies ◽  
Immune Escape Mechanisms

Platelets in cancer development and diagnosis

2018 ◽  
Vol 46 (6) ◽  
pp. 1517-1527 ◽  
Author(s):  
Annalisa Contursi ◽  
Rosalia Grande ◽  
Melania Dovizio ◽  
Annalisa Bruno ◽  
Rosa Fullone ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Immune Escape ◽  
Genetic Material ◽  
Antiplatelet Agents ◽  
Therapeutic Drug ◽  
Target Cells ◽  
Tumor Immune Escape ◽  
New Strategy ◽  
Tumor Drugs

Platelets are involved in the development and progression of cancer through several mechanisms. Platelet activation at the site of tissue damage contributes to the initiation of a cascade of events which promote tumorigenesis. In fact, platelets release a wide array of proteins, including growth and angiogenic factors, lipids and extracellular vesicles rich in genetic material, which can mediate the induction of phenotypic changes in target cells, such as immune, stromal and tumor cells, and promote carcinogenesis and metastasis formation. Importantly, the role of platelets in tumor immune escape has been described. These lines of evidence open the way to novel strategies to fight cancer based on the use of antiplatelet agents. In addition to their ability to release factors, platelets are able of up-taking proteins and genetic material present in the bloodstream. Platelets are like ‘sentinels’ of the disease state. The evaluation of proteomics and transcriptomics signature of platelets and platelet-derived microparticles could represent a new strategy for the development of biomarkers for early cancer detection and/or therapeutic drug monitoring in cancer chemotherapy. Owing to the ability of platelets to interact with cancer cells and to deliver their cargo, platelets have been proposed as a ‘biomimetic drug delivery system’ for anti-tumor drugs to prevent the occurrence of off-target adverse events associated with the use of traditional chemotherapy.

scholarly journals Cancer Stem Cell Immunology: Key to Understanding Tumorigenesis and Tumor Immune Escape?

2014 ◽  
Vol 5 ◽  
Author(s):  
Valentin S. Bruttel ◽  
Jörg Wischhusen
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Immune Escape ◽  
Tumor Immune Escape

scholarly journals Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients

2015 ◽  
Vol 5 (3) ◽  
pp. e1094598 ◽  
Author(s):  
Shaodong Hong ◽  
Nan Chen ◽  
Wenfeng Fang ◽  
Jianhua Zhan ◽  
Qing Liu ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Immune Escape ◽  
Immune Therapy ◽  
Alk Positive ◽  
Nsclc Patients

The role of mRNA translational control in tumor immune escape and immunotherapy resistance

2021 ◽  
pp. canres.1466.2021
Author(s):  
Michaël Cerezo ◽  
Caroline Robert ◽  
Lunxu Liu ◽  
Shensi Shen
Keyword(s):  
Translational Control ◽  
Immune Escape ◽  
Tumor Immune Escape

Study on mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia

2020 ◽  
Author(s):  
qiong Ning ◽  
xiangxin li ◽  
Xiangdong Jian ◽  
Xiaopeng He
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Serum Levels ◽  
Control Group ◽  
M2 Macrophages ◽  
Experimental Group ◽  
Group Serum ◽  
Acute Myeloid

Abstract To study the mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia (AML), to provide potential targets of clinical monitoring and intervention of hematological toxicity in benzene-induced AML . C3H/He mice were randomly divided into control group and experimental group. Serum levels of IL-12 in the experimental group were significantly lower than that in the control group. Serum levels of TGF-β1 in the experimental group were significantly higher than that in the control group( p <0.05). The proportion of Tim-3 positive CD14 + monocytes of bone marrow and spleen in the experimental group were both significantly higher than that in the control group ( p <0.05) by Flow cytometry (FCM). Compared with the control group, the expression of Tim-3 on (M1+M2) macrophages of bone marrow in the experimental group significantly increased by immunofluorescence assay. The expression of type M2 macrophages in (M1+M2) macrophages of bone marrow and spleen tissues in the experimental group were both higher than that in the control group. The expression levels of p-PI3K, p-AKT and p-mTOR in the experimental group were all significantly higher than that in the control group. Tim-3 was highly expressed in macrophages in benzene-induced AML. It promoted the activation of PI3K/AKT/mTOR signaling pathway, stimulated the secretion of anti-inflammatory cytokines, and inhibited the secretion of pro-inflammatory cytokines. High expression of Tim-3 changed the phenotype and function of macrophages by promoting the macrophages polarization, thus inducing negative immune response in the tumor microenvironment and tumor immune escape.

scholarly journals Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein

2020 ◽  
Vol 8 (1) ◽  
pp. e000233 ◽  
Author(s):  
Nicolas Torres ◽  
María Victoria Regge ◽  
Florencia Secchiari ◽  
Adrián David Friedrich ◽  
Raúl Germán Spallanzani ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Antitumor Immunity ◽  
Immune Escape ◽  
Chimeric Protein ◽  
Antitumor Effects ◽  
Tumor Immune Escape ◽  
Mouse Tumors ◽  
Antitumor Vaccine ◽  
Dependent Cell ◽  
Underlying Mechanisms

BackgroundNatural killer and cytotoxic CD8+T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). Both molecules are overexpressed on a great variety of tumors from different tissues, making them attractive targets for immunotherapy. However, tumors shed MICA and MICB, and the soluble forms of both (sMICA and sMICB) mediate tumor-immune escape. Some reports indicate that anti-MICA antibodies (Ab) can promote the restoration of antitumor immunity through the induction of direct antitumor effects (antibody-dependent cell-mediated cytotoxicity, ADCC) and scavenging of sMICA. Therefore, we reasoned that an active induction of anti-MICA Ab with an immunogenic protein might represent a novel therapeutic and prophylactic alternative to restore antitumor immunity.MethodsWe generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase fromBrucellaspp (BLS) and used it to generate anti-MICA polyclonal Ab (pAb) and to investigate if these anti-MICA Ab can reinstate antitumor immunity in mice using two different mouse tumors engineered to express MICA. We also explored the underlying mechanisms of this expected therapeutic effect.ResultsImmunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8+T cell recruitment.ConclusionsImmunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.

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