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Abstract：
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4). PD-L1 - PD-1 ligand- expression on cancer lung adenocarcinoma and melanoma is associated with an improved clinical response to anti-PD-1/PD-L1. Nevertheless, a standardization of the biological assays is needed before a clinical translation. CD8-T cell tumor infiltration seems to be a prerequisite to an optimal clinical response after anti-PD-1/PD-L1 administration. In situ high mutational load is associated with a CD8-T cell infiltration and a higher rate of anti-PD-1 and anti-CTLA-4 response. If we consider a more holistic approach, the role of the gut microbiota in the response to these treatments is now well established in pre-clinical experiments. The universal marker is not identified so far, but the reliable marker should be in the tumor compartment and combining multiples markers could be suitable to predict response in different contexts.
摘要：
针对共抑制受体的免疫疗法最近开辟了一种新的有希望的癌症治疗方法。的确,在许多适应症中,抗CTLA-4和抗PD-1治疗后观察到客观的临床缓解,但在接受治疗的病例中,治疗仍有70%~80%失败.鉴于这些疗法的副作用和高成本，有必要开发生物标志物。本综述重点关注潜在的预测性生物标志物。在外周血中，基线时高水平的IL-2可溶性受体和缺乏ICOS+CD4-T淋巴细胞诱导可能与伊匹单抗(抗CTLA-4)治疗的黑色素瘤患者没有临床反应相关.PD-L1-PD-1配体在癌症肺腺癌和黑色素瘤上的表达与抗PD-1/PD-L1的改善的临床反应相关。然而，在临床翻译之前，需要对生物学分析进行标准化。CD8-T细胞肿瘤浸润似乎是抗PD-1/PD-L1给药后最佳临床反应的先决条件。原位高突变负荷与CD8-T细胞浸润和抗PD-1和抗CTLA-4应答的较高速率相关。如果我们考虑更全面的方法，肠道微生物群在这些治疗反应中的作用现已在临床前实验中得到充分证实.到目前为止还没有发现通用标记，但可靠的标记物应该在肿瘤区室，结合多个标记物可能适合预测不同情况下的反应。
