PDX Pharmaceuticals, Inc., Portland, OR, USA.
VA Portland Health Care System, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Cancer Metastasis Rev. 2021 Jun;40(2):519-536. doi: 10.1007/s10555-021-09968-0. Epub 2021 May 7.
Increased levels of total tumor-infiltrating lymphocytes (TILs) are generally associated with good prognosis in several breast cancer subtypes. Subtypes of TILs impact both tumor cells and immune cells in a variety of different ways, leading to either a pro-tumor or antitumor effect. Tumor-infiltrating CD8 T cells and natural killer (NK) cells perform as effector cells against tumor cells and are associated with better clinical outcome. Immunotherapy approaches that improve the antitumor activity and proliferation of CD8 T and NK cells include PD-1/PD-L1 blockade, CAR T cell therapy, or ex vivo-stimulated NK cells. A subset of CD8 T cells, tissue-resident memory T cells, has also recently been associated with good prognosis in breast cancer patients, and has potential to serve as a predictive biomarker and therapeutic target. Tumor-infiltrating B cells also secrete apoptosis-inducing IgG antibodies and can act as antigen-presenting cells to prime CD4 and CD8 T cells. On the other hand, regulatory T and regulatory B cells modulate the immune response from CD8 T cells and NK cells by secreting immunosuppressive cytokines and inhibiting maturation of antigen-presenting cells (APCs). These regulatory cells are typically associated with poor prognosis, therefore rendering suppression of their regulatory function a key immunotherapeutic strategy.
肿瘤浸润淋巴细胞(TILs)水平升高通常与几种乳腺癌亚型的良好预后相关。TIL 亚型以各种不同的方式影响肿瘤细胞和免疫细胞,导致促肿瘤或抗肿瘤效应。肿瘤浸润 CD8 T 细胞和自然杀伤(NK)细胞作为效应细胞对抗肿瘤细胞,并与更好的临床结果相关。提高 CD8 T 和 NK 细胞抗肿瘤活性和增殖的免疫疗法方法包括 PD-1/PD-L1 阻断、嵌合抗原受体 T 细胞疗法或体外刺激的 NK 细胞。最近,CD8 T 细胞的一个亚群——组织驻留记忆 T 细胞也与乳腺癌患者的良好预后相关,并有可能成为预测生物标志物和治疗靶点。肿瘤浸润 B 细胞也分泌凋亡诱导 IgG 抗体,并可作为抗原呈递细胞来激活 CD4 和 CD8 T 细胞。另一方面,调节性 T 和 B 细胞通过分泌免疫抑制细胞因子和抑制抗原呈递细胞(APC)的成熟来调节 CD8 T 细胞和 NK 细胞的免疫反应。这些调节细胞通常与预后不良相关,因此抑制其调节功能是一种关键的免疫治疗策略。
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