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Introduction
The development of cancer in humans is a multistep programmed process that involves multiple gene mutations and genetic modifications and leads to uncontrolled cell division and apoptosis evasion. The accumulation of gene mutations results in the expression of tumor antigens, triggering the activation of innate and adaptive antitumor immune responses aimed at eliminating tumor cells (1). The tumor microenvironment (TME), a new concept for developing tumor markers, has been proposed and widely recognized for its important role (2). The dynamic interaction between tumor cells and immune cells controls tumorigenesis, local invasion and distant metastasis. Immune cells remain in situ or migrate as a response to different signals, further contributing to the formation of the overall TME (1).
The immune system of the host is the main target for antitumor immunotherapy. The accumulation of tumor immune cells contributing to tumor resistance is an important part of tumor genetics (3). There are several types of tumor-infiltrating immune cells, including T cells, B cells, dendritic cells (DCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells. A core component of tumorigenesis is dysregulation of the immune system (4,5). Tumor cells attempt to escape immune surveillance in different ways, resulting in ineffective immune surveillance. Immune cells provide a microenvironment for developing inflammation and tumor metastasis. Therefore, the basic strategy of tumor immunotherapy is always focused on how to avoid impaired immune surveillance and how to prevent damage to the immune system (6). The most typical example is the finding that the tumor-promoting function of regulatory/immunosuppressive immune cells depends on the inflammatory environment mediated by inflammatory cells, which can aggregate and alternately induce TAMs, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) (7–9). Therefore, achieving a comprehensive understanding of the TME is crucial.
T-cell-related pathways play an important role in immunotherapy and have been used for targeted tumor therapies, such as anti-programmed death 1, anti-programmed death ligand 1 (PD-L1), anti-cytotoxic T lymphocyte antigen-4 and chimeric antigen receptor T-cell therapy (10). Numerous studies have reported that the expression of PD-L1 is an independent risk factor for progression-free survival (PFS) and overall survival (OS) in patients with cancer and is negatively associated with CD8+ tumor-infiltrating lymphocytes (TILs) (10–13). It is generally believed that the typical T-cell-mediated antitumor immune...