The soldiers needed to be awakened: Tumor-infiltrating immune cells

Abstract

In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

Keywords: antigen presentations; immunotherapy; tertiary lymphoid structures; tumor microenvironment; tumor-infiltrating immune cells.

FIGURE 1

Patients with cancer have different prognosis due to TLS heterogeneity. Compared to stromal TLS, intratumoral or both intratumoral and peritumoral mature TLSs were associated with a better prognosis in different tumors. TLSs with GCs have been shown to kill tumor cells more effectively than immature TLS. PDAC: pancreatic ductal adenocarcinoma; HCC: hepatocellular carcinoma; CRC: colorectal cancer; ccRCC: clear cell renal cell carcinomas; DC-LAMP: Dendritic dendritic Cell cell Lysosomelysosome-–Associated associated Membrane membrane Proteinprotein; FDC: follicular dendritic cells; HEV: high endothelial venules.

FIGURE 2

Tumor-infiltrating immune cells are important. Different cells play different roles. CD8+ T cell, CD8 TRM, and NK could kill tumor cells. Bregs, Tregs, MDSCs, and M2-TAM promote tumor cell growth. Tumor cells also secrete various molecules to disturb immune cell function. These molecules can convert cell phenotype and change their function, like NK cells. Specially, TGF-β derived from tumor cells could promote the function of CD8 TRM and Tfh cells. The crosstalk of these immune cells are is important for their function. Inhibitory cells secrete various immunosuppressive molecules to impair the cytotoxicity of effector cells. CD8 TRM: CD8 tissue resident memory; DC: dendritic cell; cDCs: conventional dendritic cells; pDCs: plasmacytoid DCs; Tfh: T follicular cell; NK: natural killer; hILC: helper innate lymphoid cells; Bregs: regulatory B cells; Tregs: regulatory T cells; MDSC: myeloid-derived suppressor cell; M2-TAM: M2 macrophages; EMT: epithelial mesenchymal transition.