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.
Keywords: Cancer, chemotherapy, tumor-associated macrophages, intratumor heterogeneity, tumor microenvironment, personalized therapy.
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