Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA, USA.
Adv Exp Med Biol. 2021;1302:99-111. doi: 10.1007/978-3-030-62658-7_8.
Multiple checkpoint mechanisms are overridden by cancer cells in order to develop into a tumor. Neoplastic cells, while constantly changing during the course of cancer progression, also craft their surroundings to meet their growing needs. This crafting involves changing cell surface receptors, affecting response to extracellular signals and secretion of signals that affect the nearby cells and extracellular matrix architecture. This chapter briefly comprehends the non-cancer cells facilitating the cancer growth and elaborates on the notable role of the CCR9-CCL25 chemokine axis in shaping the tumor microenvironment (TME), directly and via immune cells. Association of increased CCR9 and CCL25 levels in various tumors has demonstrated the significance of this axis as a tool commonly used by cancer to flourish. It is involved in attracting immune cells in the tumor and determining their fate via various direct and indirect mechanisms and, leaning the TME toward immunosuppressive state. Besides, elevated CCR9-CCL25 signaling allows survival and rapid proliferation of cancer cells in an otherwise repressive environment. It modulates the intra- and extracellular protein matrix to instigate tumor dissemination and creates a supportive metastatic niche at the secondary sites. Lastly, this chapter abridges the latest research efforts and challenges in using the CCR9-CCL25 axis as a cancer-specific target.
为了发展成肿瘤，癌细胞会绕过多个检查点机制。在癌症进展过程中不断变化的肿瘤细胞，也会塑造其周围环境以满足其不断增长的需求。这种塑造涉及改变细胞表面受体，影响对细胞外信号的反应以及分泌影响附近细胞和细胞外基质结构的信号。本章简要概述了促进癌症生长的非癌细胞，并详细阐述了 CCR9-CCL25 趋化因子轴在塑造肿瘤微环境 (TME) 中的重要作用，包括直接作用和通过免疫细胞的间接作用。在各种肿瘤中观察到 CCR9 和 CCL25 水平的增加，表明该轴作为癌症常用的工具具有重要意义。它参与吸引肿瘤中的免疫细胞，并通过各种直接和间接机制决定其命运，使 TME 向免疫抑制状态倾斜。此外，升高的 CCR9-CCL25 信号允许在 otherwise 抑制性环境中癌细胞的存活和快速增殖。它调节细胞内外的蛋白质基质，引发肿瘤扩散，并在继发性部位创建支持转移的生态位。最后，本章概述了利用 CCR9-CCL25 轴作为癌症特异性靶点的最新研究进展和挑战。
