A commentary on: "A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells" - tumor microenvironment: the Achilles heel of cancer.

Abstract

Cancer is a complicated disease. With the deepening of the research on the mechanism of tumor initiation, promotion and progression in recent years, researchers have gradually shifted their focus from tumor itself to TME. The concept of TME can be traced back to the relationship between tumor and inflammation and the theory of “seed and soil” in the latter half of the nineteenth century [1]. TME consists of non-malignant cells, vessels, lymph nodes, nerves, intercellular components, and metabolites located at the center, margin, or periphery of the tumor [1]. There is increasing evidence that cellular and non-cellular components of the TME can promote tumor initiation, growth, invasion, metastasis, and response to treatment. The TME is composed of three main cell types: immune cells, stromal cells (e.g. cancer-associated fibroblasts), vascular cells [2, 3]. For the past few years, the interaction between tumor cells and immune cells has been gradually recognized. Tumors are known to change markedly in terms of the quantity and phenotypes of immune and stromal cells in the TME [3]. TME is highly heterogeneous across different patients, and the plasticity of immune cells is an important part of tumor heterogeneity. The immunosuppression after immune evasion becomes a new hallmark of cancer [2]. The infiltration of immune cells in TME, located at the core or margin of tumor, the adjacent lymphoid organ or lymph nodes (also called tertiary lymphoid structures), is closely related to the prognosis of cancer [1]. Immune cells in TME can be divided into lymphocytes andmyeloid cells according to their diverse developmental lineages. Immunosuppressive myeloid cells are one of the major obstacles to cancer immunotherapy. At present, although several therapeutic approaches targeting myeloid cells are being tested in preclinical and clinical studies, the study of lymphocytes is relatively in-depth [4]. Tumor‐infiltrating lymphocytes consist of all lymphocytic cell populations that have invaded the tumor tissue, including T cells, B cells, plasma cells and natural killer (NK) cells. T cell‐mediated adaptive immunity is considered to play a major role in anti‐tumor immunity [5]. According to function, immune cells can be classified as tumor-antagonizing and tumor-promoting immune cells. The tumor-antagonizing immune cells mainly consist of effector T cells (including CD8+ cytotoxic T cells and effector CD4+ T cells), NK cells, dendritic cells (DCs), M1-like macrophages and N1-like neutrophils [2]. The CD8+ cytotoxic T cells are considered to be the major subset of lymphocytes that kill cancer cells. NK cells are also one important subset of tumor-antagonizing immune cells that mediate the immunosurveillance of tumor [2]. On the other hand, T regulatory cells (Tregs) are able to inhibit the immune response mediated by CD4+ and CD8+ T cells, by suppressing T cell proliferation, antigen presentation, and cytokine production [6]. The recent single-cell sequencing revealed that T cells are highly heterogeneous and T cell states associated with the prognosis of patients and therapy response [7]. In a part of tumors, the tumor cells would inhibit the activation of cytotoxic T cells via expressing *Corresponding authors: Zhaode Bu and Jiafu Ji, Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China, E-mail: buzhaode@cjcrcn.org (Z. Bu), jijiafu@hsc.pku.edu.cn (J. Ji) Jingtao Wei, Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China. https:// orcid.org/0000-0001-8260-1835 Med. Rev. 2021; 1(2): 126–128