Department of Tissues and Organs Transplantation and Cellular Therapies, D.E.O.T., University of Bari "Aldo Moro", Piazza G. Cesare, 11-Policlinico 70124 Bari, Italy.
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", Via E. Orabona, 4, 70125 Bari, Italy.
Int J Mol Sci. 2019 May 15;20(10):2401. doi: 10.3390/ijms20102401.
The tumor microenvironment plays a pillar role in the progression and the distance dissemination of cancer cells in the main malignancies affecting women-epithelial ovarian cancer, endometrial cancer and cervical cancer. Their acquires specific properties thanks to intense crosstalk between stromal and cancer cells, leading to a vicious circle. Fibroblasts, pericytes, lymphocytes and tumor associated-macrophages orchestrate most of the biological pathways. In epithelial ovarian cancer, high rates of activated pericytes determine a poorer prognosis, defining a common signature promoting ovarian cancer proliferation, local invasion and distant spread. Mesenchymal cells also release chemokines and cytokines under hormonal influence, such as estrogens that drive most of the endometrial cancers. Interestingly, the architecture of the cervical cancer is shaped by the synergy of high-risk Human Papilloma Virus oncoproteins and the activity of stromal estrogen receptor α. Lymphocytes represent a shield against cancer cells but some cell subpopulation could lead to immunosuppression, tumor growth and dissemination. Cytotoxic tumor infiltrating lymphocytes can be eluded by over-adapted cancer cells in a scenario of immune-tolerance driven by T-regulatory cells. Therefore, the tumor microenvironment has a high translational potential offering many targets for biological and immunological therapies.
肿瘤微环境在女性主要恶性肿瘤（上皮性卵巢癌、子宫内膜癌和宫颈癌）中癌细胞的进展和远处转移中起着重要作用。肿瘤微环境中的基质细胞与癌细胞之间的强烈相互作用使癌细胞获得了特定的性质，导致恶性循环。成纤维细胞、周细胞、淋巴细胞和肿瘤相关巨噬细胞协调大多数生物学途径。在上皮性卵巢癌中，高比例的活化周细胞预示着预后不良，确定了一个促进卵巢癌细胞增殖、局部侵袭和远处转移的共同特征。间质细胞也会在激素（如雌激素）的影响下释放趋化因子和细胞因子，这是大多数子宫内膜癌的驱动因素。有趣的是，高危型人乳头瘤病毒致癌蛋白与基质雌激素受体α的活性协同作用，塑造了宫颈癌的结构。淋巴细胞是癌细胞的天然屏障，但某些细胞亚群可能导致免疫抑制、肿瘤生长和扩散。在 T 调节细胞驱动的免疫耐受情况下，过度适应的癌细胞可以逃避细胞毒性肿瘤浸润淋巴细胞。因此，肿瘤微环境具有很高的转化潜力，为生物和免疫治疗提供了许多靶点。
