Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

Abstract

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

Tumor‐infiltrating M2 macrophage in pretreatment biopsy sample predicts response to chemotherapy and survival in esophageal cancer

“…M2 macrophages are a promising therapeutic target . CCR2 or CSF‐1R inhibition has been considered to prevent recruitment of M2 macrophages to the TME or proliferation of TAM .…”

“…In addition to the biological malignancy of tumor cells and the influence of genetic characteristics on sensitivity to therapeutic agents, the immune condition of the tumor microenvironment (TME), consisting of varieties of immune cells, was recently recognized to modulate the efficiency of chemotherapy . Among the components of the TME, tumor‐infiltrating macrophages (TAM) have been reported to contribute to chemoresistance by modulating the cytotoxicity of tumor‐infiltrating T cells .…”

Macrophages induce CD47 upregulation via IL-6 and correlate with poor survival in hepatocellular carcinoma patients

“…Evasion of programmed cell removal by the innate immune system plays a critical role in tumor development and progression. [5][6][7][8][9][10][11] Recent studies have revealed that tumor cells upregulate "don't-eat-me" signals to prevent phagocytosis, thus acquiring a survival advantage. [12][13][14] CD47 is an anti-phagocytic ligand broadly expressed on platelets, erythrocytes, and lymphohematopoietic cells.…”

Monocytes and cancer: promising role as a diagnostic marker and application in therapy

“…ных клеток. В настоящее время значение клеточного состава и функциональной ориентации (поляризации) опухолевого микроокружения для клинического течения онкологических заболеваний и ýффективности проводимого противоопухолевого лечения обосновано целым рядом работ [7][8][9][10][11].…”