The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment

Abstract

Recently, in the field of cancer treatment, the paradigm has changed to immunotherapy that activates the immune system to induce cancer attacks. Among them, immune checkpoint inhibitors (ICI) are attracting attention as excellent and continuous clinical results. However, it shows not only limitations such as efficacy only in some patients or some indications, but also side-effects and resistance occur. Therefore, it is necessary to understand the factors of the tumor microenvironment (TME) that affect the efficacy of immunotherapy, that is, the mechanism by which cancer grows while evading or suppressing attacks from the immune system within the TME. Tumors can evade attacks from the immune system through various mechanisms such as restricting antigen recognition, inhibiting the immune system, and inducing T cell exhaustion. In addition, tumors inhibit or evade the immune system by accumulating specific metabolites and signal factors within the TME or limiting the nutrients available to immune cells. In order to overcome the limitations of immunotherapy and develop effective cancer treatments and therapeutic strategies, an approach is needed to understand the functions of cancer and immune cells in an integrated manner based on the TME. In this review, we will examine the effects of the TME on cancer cells and immune cells, especially how cancer cells evade the immune system, and examine anti-cancer strategies based on TME.

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

“…Several mechanisms have been implicated in cancer evasion from the immune system, including an increased expression of immune checkpoints, downregulation of surface antigens on cancer cells, recruitment of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells, and secretion of toxic metabolites [ 81 ]. The gut microbiome has been recognized as a central component of immune cancer surveillance [ 82 ].…”

Comprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma

“…Genetic alterations affect the drug sensitivity of cancer to clinical treatment and therefore are potential biomarkers for drug screening (Kim and Cho, 2022;Li et al, 2022). Therefore, we question the association between mRNA expression levels of FRAS1, FREM1 and FREM2 and patient sensitivity to four common targeted therapeutic Frontiers in Pharmacology frontiersin.org drugs (sunitinib, sorafenib, axitinib and pazopanib).…”

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy

“…Anti-tumor immunity is crucial during cancer initiation, progression, and metastasis. Tumors develop multiple mechanisms to evade anti-tumor immunity depending on the level of immune infiltration in the tumor microenvironment that defines it canonically as “cold” or “hot” ( 3 ). Cold tumors are considered “immune deserts” characterized by low immune cell infiltration ( 3 ).…”

“…Tumors develop multiple mechanisms to evade anti-tumor immunity depending on the level of immune infiltration in the tumor microenvironment that defines it canonically as “cold” or “hot” ( 3 ). Cold tumors are considered “immune deserts” characterized by low immune cell infiltration ( 3 ). The decreased immunogenicity of cold tumors enables them to evade immune destruction by decreasing levels of tumor antigens, inhibiting maturation of dendritic cells, and suppressing T cell activation, infiltration, and migration ( 3 ).…”

“…Cold tumors are considered “immune deserts” characterized by low immune cell infiltration ( 3 ). The decreased immunogenicity of cold tumors enables them to evade immune destruction by decreasing levels of tumor antigens, inhibiting maturation of dendritic cells, and suppressing T cell activation, infiltration, and migration ( 3 ). Hot tumors are highly infiltrated by immune cells; however, they evade anti-tumor immunity through impaired T cell tumor recognition, increased immune suppressor cell activation, and increased expression of inhibitory immune checkpoint molecules such as programmed death-ligand 1 (PD-L1) ( 3 ).…”