Multifaceted Roles of Chemokines and Chemokine Receptors in Tumor Immunity

Abstract

Various immune cells are involved in host tumor immune responses. In particular, there are many T cell subsets with different roles in tumor immunity. T-helper (Th) 1 cells are involved in cellular immunity and thus play the major role in host anti-tumor immunity by inducing and activating cytotoxic T lymphocytes (CTLs). On the other hand, Th2 cells are involved in humoral immunity and suppressive to Th1 responses. Regulatory T (Treg) cells negatively regulate immune responses and contribute to immune evasion of tumor cells. Th17 cells are involved in inflammatory responses and may play a role in tumor progression. However, recent studies have also shown that Th17 cells are capable of directly inducting CTLs and thus may promote anti-tumor immunity. Besides these T cell subsets, there are many other innate immune cells such as dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs) that are involved in host immune responses to cancer. The migratory properties of various immune cells are critical for their functions and largely regulated by the chemokine superfamily. Thus, chemokines and chemokine receptors play vital roles in the orchestration of host immune responses to cancer. In this review, we overview the various immune cells involved in host responses to cancer and their migratory properties regulated by the chemokine superfamily. Understanding the roles of chemokines and chemokine receptors in host immune responses to cancer may provide new therapeutic opportunities for cancer immunotherapy.

Deep Learning Explains the Biology of Branched Glycans from Single-Cell Sequencing Data

“…Well-established suppressive immune checkpoint receptors were within the top 50 genes, such as Lag3 , Ctla4 , Pdcd1 , and Tigit (Figure 5D). We also found other highly ranked SHAP genes known for predominantly immunosuppressive roles in T cells, including: (i) genes of the killer cell lectin-like receptor family such as Klrc1 (0.31%) and Klrg1 (0.50%) (Huot et al, 2021; Li et al, 2016); (ii) chemokines and chemokine receptors such as Ccl5 (0.10%), Ccr5 (0.21%), and Ccr2 (0.33%) (Aldinucci and Casagrande, 2018; Matsuo et al, 2021; Tu et al, 2020; Zeng et al, 2022); (iii) other genes such as Fgl2 (0.64%) and Lgals1 (1.06%) (Corapi et al, 2018; Hou et al, 2021) (Figure 5D). Overall, SHAP genes had substantial overlap with genes known to be implicated in the biology of branched glycans.…”

“…Therefore, the CCL2/CCR2 axis may be an alternative mechanism to regulate MGAT5/β1,6-branched glycans in immune cells. In line with the immunosuppressive role of β1,6-branched glycans, CCL2 secreted by cancer cells contributes to an immunosuppressive tumor microenvironment, and blockade of CCR2 in mice improved the efficacy of immune checkpoint therapy (Matsuo et al, 2021;Tu et al, 2020), suggesting a direct biomedically relevant role of this glycan feature.…”

“…(i) genes of the killer cell lectin-like receptor family such as Klrc1 (0.31%) and Klrg1 (0.50%) (Huot et al, 2021;Li et al, 2016); (ii) chemokines and chemokine receptors such as Ccl5 (0.10%), Ccr5 (0.21%), and Ccr2 (0.33%) (Aldinucci and Casagrande, 2018;Matsuo et al, 2021;Tu et al, 2020;Zeng et al, 2022); (iii) other genes such as Fgl2 (0.64%) and Lgals1…”

Novel Hypoxia-Associated Gene Signature Depicts Tumor Immune Microenvironment and Predicts Prognosis of Colon Cancer Patients

“…Next, we found that most chemokines, including CXCL5, 6, 8, 9, 10, 11, and 12, CCL1, 2, 3, 4, 7, 8, 11, 12, 13, 19, 21, 23, 26, and 28, were significantly highly expressed in HS ( Figures 7G,H ). Other studies revealed that the upregulated expression of chemokines, including CXC and CC chemokine families, could impede the TILs infiltrating into a tumor, support the growth of malignant cells, and facilitate the migration of myeloid-derived suppressor cells (MDSCs), which would cause the drug resistance to the chemotherapy and immunotherapy ( Korbecki et al, 2020 ; Bullock and Richmond, 2021 ; Matsuo et al, 2021 ).…”

Emerging Roles of Chemokines in Cancer Immunotherapy

“…The 11 review articles written by chemokine specialists provide a cross-section of current tumor-related chemokine research and underscore the multiple and in part overlapping functions assigned to chemokines in cancer. Chemokines are instrumental in defining the immune infiltrate, including anti-tumor effector T cells as well as tumor-promoting Treg cells, macrophages, myeloid-derived suppressor cells (MDSC) and neutrophils [ 5 ]. On the same line of thought, it has been suggested that certain chemokines could be exploited to turn a “cold” tumor into a “hot” tumor characterized by T-cell infiltrates that could be targeted by immunomodulatory agents [ 6 ].…”