Introduction

Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy.

Materials and methods

Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed.

Results

The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis.

Conclusions

Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.

中文翻译：

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肿瘤浸润淋巴细胞、PD-L1 和 MMR 缺陷的联合表征可能会识别出可从免疫治疗中受益的直肠癌患者亚组

介绍

错配修复缺陷、免疫生育力和 PD-L1 表达状态是决定肿瘤对免疫治疗反应以及最终预后的关键组织病理学和分子特征。这些研究是在一系列接受术后化疗和放疗的局部晚期直肠癌患者中进行的。

材料和方法

在苏木精-伊红组织切片中评估肿瘤浸润淋巴细胞（TIL）密度。通过免疫组织化学评估 PD-L1 表达和 MMR 蛋白（MLH1、PSM2、MSH2 和 MSH6）的表达。评估了它们与组织病理学变量（淋巴结受累和肿瘤出芽）和预后的关联。

结果

侵入肿瘤前沿的 TIL 密度显着较高，与肿瘤出芽呈负相关，并与更好的总生存期 (OS) 和无远处转移生存期 (DMFS) 直接相关（分别为 p = 0.02 和 0.02）。癌细胞 PD-L1 表达与高 TIL 密度相关 (p < 0.01)，但与预后无关，尽管其过度表达定义了高 TIL 密度患者 OS 较差的趋势。基质浸润免疫细胞的高 PD-L1 表达与更好的 OS 和 DMFS 相关（分别为 p = 0.007 和 0.001。26.2% 的病例记录到 MMR 缺陷，这与较高的 TIL 密度相关，但与预后无关。

结论

致密的肿瘤内淋巴细胞浸润与直肠癌更好的预后有关，尽管它也与 PD-L1 表达相关，而 PD-L1 表达可能会对 TIL 的抗肿瘤作用产生不利影响。后一亚组患者（高 TIL 密度/高癌细胞 PD-L1 表达）可能与已建立的 MMR 缺陷患者亚组一起成为抗 PD-1/PD-L1 免疫治疗的额外靶点。