CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases.
Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases.
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尽管我们的研究队列有限，但我们已经表明，在 c-CCCs 中可不同程度地发现 PD-L1 表达和 MMR 缺陷。
宫颈管透明细胞癌（c-CCC）是一种罕见且不依赖 HPV 的宫颈腺癌，通常对常规化疗耐药。近年来，免疫疗法被纳入 PD-L1 阳性或错配修复（MMR）缺陷宫颈癌的优选二线治疗方案。本研究评估 c-CCC 的临床病理特征、PD-L1 表达和 MMR 缺陷状态。
研究纳入 16 例确诊 c-CCC 病例。采用两种不同的 PD-L1 克隆抗体（22C3 和 SP263）评估 PD-L1 表达，并使用 4 种 MMR 蛋白（MLH1、PMS2、MSH2 和 MSH6）评估 MMR 缺陷状态。
多数 c-CCC 病例为 FIGO I 期（68.75%）。采用 22C3 和 SP263 克隆检测时，分别有 62.5%（10/16）和 69%（11/16）的病例在肿瘤细胞或肿瘤浸润免疫细胞（TIL）中表达 PD-L1。多数 TIL 密度较高病例也呈 PD-L1 阳性。多数病例 PD-L1 表达率低于 50%，另有 12.5% 病例显示广泛 PD-L1 染色。总体而言，31.25% 的病例存在 MMR 缺陷；其中多数（80%）为 PD-L1 阳性。
尽管本研究队列规模有限，但结果显示 c-CCC 可不同程度地出现 PD-L1 表达和 MMR 缺陷。这提示伴随的 TIL 密度和 MMR 缺陷可作为预测 c-CCC 中 PD-L1 阳性的候选指标。不过，要明确这些发现的临床意义，还需观察接受免疫疗法病例的客观治疗结局。
Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated.
Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6).
Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive.
Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.
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