Trial watch: Prognostic and predictive value of the immune infiltrate in cancer.
Trial watch: Prognostic and predictive value of the immune infiltrate in cancer.
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DOI：
10.4161/onci.22009
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发表时间：
2012-11-01
期刊：
影响因子：
7.2
通讯作者：
Galluzzi L
中科院分区：
文献类型：
--
作者：
Senovilla L;Vacchelli E;Galon J;Adjemian S;Eggermont A;Fridman WH;Sautès-Fridman C;Ma Y;Tartour E;Zitvogel L;Kroemer G;Galluzzi L
实体瘤由多种细胞成分组成，包括真正的恶性细胞以及内皮细胞、结构细胞和免疫细胞。一方面，肿瘤间质发挥主要的促肿瘤发生和免疫抑制功能，反映了癌细胞塑造微环境以满足其自身代谢和免疫需求的能力。另一方面，有一种成分的肿瘤浸润性白细胞（TIL）已被专门招募，试图控制肿瘤生长。沿着对免疫系统在肿瘤发生、肿瘤进展和对治疗的反应中所起的关键作用的认识，免疫浸润在这种情况下的潜在预后和/或预测作用吸引了越来越多的注意力。来自大型临床研究的数据确实表明，特异性免疫细胞群（包括（但不限于）CD 8+细胞毒性T淋巴细胞、Th 1和Th 17 CD 4 + T细胞、自然杀伤细胞、树突状细胞和M1巨噬细胞）对肿瘤病变的稳健浸润构成了几种类型癌症的独立预后指标。相反，肿瘤内高水平的CD 4 + CD 25 + FOXP 3+调节性T细胞、Th 2 CD 4 + T细胞、髓源性抑制细胞、M2巨噬细胞和中性粒细胞通常与预后不良相关。到目前为止，只有少数研究已经解决了TIL在癌症患者中的真正预测潜力，通常令人欣慰的是，至少在某些临床环境中，免疫浸润可以可靠地预测特定患者是否会对治疗产生反应。在本试验观察中，我们将总结临床试验的结果，这些临床试验已经评估/正在评估实体恶性肿瘤背景下免疫浸润的预后和预测价值。
Solid tumors are constituted of a variety of cellular components, including bona fide malignant cells as well as endothelial, structural and immune cells. On one hand, the tumor stroma exerts major pro-tumorigenic and immunosuppressive functions, reflecting the capacity of cancer cells to shape the microenvironment to satisfy their own metabolic and immunological needs. On the other hand, there is a component of tumor-infiltrating leucocytes (TILs) that has been specifically recruited in the attempt to control tumor growth. Along with the recognition of the critical role played by the immune system in oncogenesis, tumor progression and response to therapy, increasing attention has been attracted by the potential prognostic and/or predictive role of the immune infiltrate in this setting. Data from large clinical studies demonstrate indeed that a robust infiltration of neoplastic lesions by specific immune cell populations, including (but not limited to) CD8+ cytotoxic T lymphocytes, Th1 and Th17 CD4+ T cells, natural killer cells, dendritic cells, and M1 macrophages constitutes an independent prognostic indicator in several types of cancer. Conversely, high levels of intratumoral CD4+CD25+FOXP3+ regulatory T cells, Th2 CD4+ T cells, myeloid-derived suppressor cells, M2 macrophages and neutrophils have frequently been associated with dismal prognosis. So far, only a few studies have addressed the true predictive potential of TILs in cancer patients, generally comforting the notion that—at least in some clinical settings—the immune infiltrate can reliably predict if a specific patient will respond to therapy or not. In this Trial Watch, we will summarize the results of clinical trials that have evaluated/are evaluating the prognostic and predictive value of the immune infiltrate in the context of solid malignancies.