CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Loss of Major Histocompatibility Complex Class I, CD8 + Tumor-infiltrating Lymphocytes, and PD-L1 Expression in Ovarian Clear Cell Carcinoma.
Loss of Major Histocompatibility Complex Class I, CD8 + Tumor-infiltrating Lymphocytes, and PD-L1 Expression in Ovarian Clear Cell Carcinoma.
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卵巢透明细胞癌（OCCC）是一种化疗耐药的卵巢癌，对抗程序性死亡-1/程序性死亡配体-1（PD-1/PD-L1）治疗反应有限。抗PD-1/PD-L1治疗的效果依赖于细胞毒性T细胞反应，而该反应由主要组织相容性复合体（MHC）I类分子介导的抗原呈递所触发。MHC I类分子缺失同时伴PD-L1表达已在多种癌症类型中被注意到；然而，这些发现及其预后价值在OCCC中很少被评估。
我们收集了76例OCCC患者的数据进行临床病理分析。MHC I类分子表达缺失见于44.7%的病例，包括39.3%至47.4%的PD-L1+病例，并与较少的CD8+TIL（肿瘤浸润淋巴细胞）（TILs）相关。PD-L1阳性与较多的CD8+TILs相关。Cox比例风险模型显示，高（≥50/mm2）CD8+TILs与较短疾病特异性生存期（风险比[HR]=3.447，95%置信区间[CI]：1.222-9.720，P=0.019）和总生存期（HR=3.053，95%CI：1.105-8.43，P=0.031）相关。使用联合阳性评分判定PD-L1阳性与较短无进展生存期（HR=3.246，95%CI：1.435-7.339，P=0.005）、疾病特异性生存期（HR=4.124，95%CI：1.403-12.116，P=0.010）和总生存期（HR=4.489，95%CI：1.553-12.972，P=0.006）相关。MHC I类分子缺失可能促进OCCC中的免疫逃逸和对anti-PD-1/PD-L1治疗的耐药，而CD8+TILs和使用联合阳性评分判定的PD-L1阳性可能具有负向预后价值。
Ovarian clear cell carcinoma (OCCC), a chemoresistant ovarian cancer, shows a modest response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies. The effects of anti-PD-1/PD-L1 therapies rely on cytotoxic T-cell response, which is triggered by antigen presentation mediated by major histocompatibility complex (MHC) class I. The loss of MHC class I with simultaneous PD-L1 expression has been noted in several cancer types; however, these findings and their prognostic value have rarely been evaluated in OCCC.
We collected data from 76 patients with OCCC for clinicopathologic analysis. Loss of MHC class I expression was seen in 44. 7% of the cases including 39. 3% to 47. 4% of the PD-L1 + cases and was associated with fewer CD8 + tumor-infiltrating lymphocytes (TILs). PD-L1 positivity was associated with a higher number of CD8 + TILs. Cox proportional hazard models showed that high (≥50/mm 2 ) CD8 + TILs was associated with shorter disease-specific survival (hazard ratio [HR]=3. 447, 95% confidence interval [CI]: 1. 222-9. 720, P =0. 019) and overall survival (HR=3.
053, 95% CI: 1. 105-8. 43, P =0. 031). PD-L1 positivity using Combined Positive Score was associated with shorter progression-free survival (HR=3. 246, 95% CI: 1. 435-7. 339, P =0. 005), disease-specific survival (HR=4. 124, 95% CI: 1. 403-12. 116, P =0. 010), and overall survival (HR=4. 489, 95% CI: 1. 553-12. 972, P =0. 006). Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC, and CD8 + TILs and PD-L1 positivity using Combined Positive Score may have a negative prognostic value.
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