Tumor accomplice: T cell exhaustion induced by chronic inflammation

Abstract

The development and response to treatment of tumor are modulated by inflammation, and chronic inflammation promotes tumor progression and therapy resistance. This article summarizes the dynamic evolution of inflammation from acute to chronic in the process of tumor development, and its effect on T cells from activation to the promotion of exhaustion. We review the mechanisms by which inflammatory cells and inflammatory cytokines regulate T cell exhaustion and methods for targeting chronic inflammation to improve the efficacy of immunotherapy. It is great significance to refer to the specific state of inflammation and T cells at different stages of tumor development for accurate clinical decision-making of immunotherapy and improving the efficiency of tumor immunotherapy.

Tumor-Induced T Cell Polarization by Schwann Cells

“…Although CD73 is essential to control inflammation under normal circumstances, it can support epithelial-to-mesenchymal transition, cell invasion, and angiogenesis in the context of the tumor microenvironment [ 49 ]. SC-induced T cell exhaustion seen as poor effector function and sustained expression of inhibitory receptors, may be an additional route of generation of a state of T cell dysfunction observed in chronic infection, chronic inflammation, and cancer [ 50 , 51 ]. Tumor-associated immunosuppression, including T cell exhaustion, continues to be a major barrier for effective cancer immunotherapy.…”

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

“…Our study found that CuRGcluster C, geneCluster B, and high-CuRGscore groups represented TEX characteristics with poor prognosis. TEX is also regulated by a network of transcription factors and multiple inflammatory factors ( Collins and Henderson, 2014 ; Fang et al, 2022 ). For example, high expression levels of EOMES could accelerate the exhaustion of anti-tumor CD8 + T cells ( Li et al, 2018 ).…”

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…Immune exhaustion in adaptation to persistent inflammatory stimulation is a common mechanism underlying the escape of leukemic clones from immune surveillance ( 17 , 18 ). Hyporesponsiveness is characterized by a high infiltration of negative immune cells, excessive secretion of anti-inflammatory cytokines by immune regulatory cells, and high expression of immune checkpoint molecules on tumor cells in the tumor microenvironment, which work to limit the magnitude of inflammatory responses, avoid excessive tissue damage, and maintain a dynamic immune balance in the context of chronic inflammatory stressors ( 272 , 273 ). In an immune exhaustion state, dampened antileukemic immunity favors leukemic cell escape from immunological attack and facilitates the penetration of symptomatic MNs.…”

“…A reasonable explanation is that, similar to the microenvironment in solid tumors ( 233 , 234 , 272 , 279 ), primary autoimmune pathogenesis targets specific antigens or DAMPs on HPCs or other blood cells in the BM, regardless of whether the targeted antigens are infectious ( 84 – 87 ) or neoplastic ( 95 – 102 ). Interactions between autoimmune CTLs and targeted antigens ( 50 , 59 , 100 , 232 ) or between innate immune cells and DAMPs ( 95 – 98 ) evoke an inflammatory background in the BME ( 27 , 93 , 94 , 236 ), which determines the BM-predominant autoimmunity.…”