Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

Abstract

Immunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.

Identification of a prognostic immune signature for esophageal squamous cell carcinoma to predict survival and inflammatory landscapes

“…These ndings hold broad implications for patients with cancer. We also found higher in ltration of Tregs in high-risk patients.Tregs are well-known mediators that contribute to immunologic tolerance, weakening T cell activation, and responsiveness [52,53]. All these ndings remind us that high-risk cases are more likely to pro t from immunotherapies.…”

Comprehensive Analysis of the Tumor Microenvironment in Cutaneous Melanoma associated with Immune Infiltration

“…Functional analysis suggested that the network is not only involved in the regulation of immune-related pathways, but also regulates tumor-intrinsic pathways in the development of cancer. Recent evidence has shown that oncogenic pathways in tumor cells can be activated to regulate the production of several chemokines and cytokines, which can either decrease the recruitment of immune cells or enhance the recruitment of immunosuppressive cells to tumor sites, contributing to immunoresistance in cancers [40]. Indeed, the MAPK pathway in BRAF V600E mutant melanoma cells contributes to comprised function of dendritic cell (DC) in the TME of CM, and the inhibition of the pathway can reverse the suppression of DC function [41].…”

From single gene analysis to single cell profiling: a new era for precision medicine

“…The constant interaction between tumor microenvironment (TME) and infiltrating cells as a driving factor affecting tumor progression or immuno-surveillance was the fil rouge of the second session. Tumor evolution is indeed controlled by a fine balance between the decrease in effector cells (such as CD8 + T-lymphocytes, natural killer -NKcells, M1-polarized tumor-associated macrophages, TAMs), endorsed by anti-tumor activity, and the increase in immuno-suppressive cells (such as T-regulatory -Treg -cells, myeloid-derived suppressor cells -MDSCs -, M2polarized TAMs), characterized by a tumor-tolerant phenotype [16]. Specific oncogenic pathways activated in solid tumors, such as β-catenin pathway [17], often dictate the type and activity of immuno-infiltrating cells, tipping the balance between an effective control of tumor progression by the host immune system and a tumorinduced immuno-suppression.…”