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PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer.
Virchows Archiv ( IF 3.4 ) Pub Date : 2020-09-11 , DOI: 10.1007/s00428-020-02922-5
Nicoletta D'Alessandris 1 , Innocenza Palaia 2 , Angelina Pernazza 3 , Federica Tomao 2 , Anna Di Pinto 2 , Lucia Musacchio 2 , Martina Leopizzi 3 , Valeria Di Maio 3 , Irene Pecorella 1 , Pierluigi Benedetti Panici 2 , Carlo Della Rocca 3
Affiliation  

Cancer immunotherapy has significantly improved the management of many malignancies in recent years. Although cervical cancer is the second most common women’s cancer in the world, there are still few information about the role of checkpoint inhibitors in this neoplasm, especially in the neoadjuvant setting. In the present study, we retrieved 38 consecutive patients with squamous cell cervical cancer who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical surgery. Pre-therapy biopsies were evaluated for the presence of tumor-infiltrating lymphocytes (TILs), including T (both cytotoxic CD8+ and helper CD4+) and B lymphocytes, macrophages, natural-killer cells, and eosinophils. Immunohistochemistry was performed to characterize the inflammatory cells and to evaluate programmed death-ligand 1 (PD-L1) expression on both neoplastic and inflammatory cells. We divided our study population in three groups using three cut-offs (< 10%, 10–40%, >40%), for both TILs and PD-L1 evaluation. Pathological response to NACT was obtained from the histological reports of the post-therapy surgical specimens. We observed that all cases showed stromal TILs, with a predominance of CD3+/CD4+ T helper cells, thus supporting the strong immunogenic potential of cervical cancer. The vast majority of neoplasms expressed PD-L1: 100% on immune cells and 92% on tumor cells. Firstly, we noticed that the percentage of neoplastic cells PD-L1+ was positively associated with high TIL percentage (p = 0.0073) and with increased PD-L1 expression on inflammatory cells (p = 0.0297). Secondly, we observed a significant correlation between both the percentage (p = 0.0105) of TILs and the expression of PD-L1 (p = 0.01045) on inflammatory cells and pathological response to NACT. These results suggest that cervical cancer could be a good target for immunotherapy, also in the neoadjuvant setting. Furthermore, PD-L1 expression was significantly associated with stromal TILs that interestingly may predict pathological response to NACT.



中文翻译:

PD-L1的表达与肿瘤浸润淋巴细胞有关,后者预测鳞状细胞宫颈癌对NACT的反应。

近年来,癌症免疫疗法已大大改善了许多恶性肿瘤的管理。尽管子宫颈癌是世界上第二大最常见的女性癌症,但是关于检查点抑制剂在这种肿瘤中,特别是在新辅助治疗中的作用的信息仍然很少。在本研究中,我们检索了38例连续的鳞状细胞宫颈癌患者,他们接受了铂类新辅助化疗(NACT),然后进行了根治性手术。评估治疗前的活检组织中是否存在肿瘤浸润淋巴细胞(TIL),包括T(细胞毒性CD8 +和辅助CD4 +)和B淋巴细胞,巨噬细胞,天然杀伤细胞和嗜酸性粒细胞。进行了免疫组织化学以表征炎性细胞并评估肿瘤性和炎性细胞上的程序性死亡配体1(PD-L1)表达。对于TIL和PD-L1评估,我们使用三个临界值(<10%,10–40%,> 40%)将研究人群分为三组。对NACT的病理反应是从治疗后手术标本的组织学报告中获得的。我们观察到,所有病例均显示出基质TIL,并以CD3 + / CD4 + T辅助细胞为主,从而支持了宫颈癌的强大免疫原性潜力。绝大多数肿瘤表达PD-L1:在免疫细胞上表达100%,在肿瘤细胞上表达92%。首先,我们注意到肿瘤细胞PD-L1 +的百分比与高TIL百分比呈正相关(对于TIL和PD-L1评估,我们使用三个临界值(<10%,10–40%,> 40%)将研究人群分为三组。对NACT的病理反应是从治疗后手术标本的组织学报告中获得的。我们观察到,所有病例均显示出基质TIL,并以CD3 + / CD4 + T辅助细胞为主,从而支持了宫颈癌的强大免疫原性潜力。绝大多数肿瘤表达PD-L1:在免疫细胞上表达100%,在肿瘤细胞上表达92%。首先,我们注意到肿瘤细胞PD-L1 +的百分比与高TIL百分比呈正相关(对于TIL和PD-L1评估,我们使用三个临界值(<10%,10–40%,> 40%)将研究人群分为三组。对NACT的病理反应是从治疗后手术标本的组织学报告中获得的。我们观察到,所有病例均显示出基质TIL,并以CD3 + / CD4 + T辅助细胞为主,从而支持了宫颈癌的强大免疫原性潜力。绝大多数肿瘤表达PD-L1:在免疫细胞上表达100%,在肿瘤细胞上表达92%。首先,我们注意到肿瘤细胞PD-L1 +的百分比与高TIL百分比呈正相关(我们观察到,所有病例均显示出基质TIL,并以CD3 + / CD4 + T辅助细胞为主,从而支持了宫颈癌的强大免疫原性潜力。绝大多数肿瘤表达PD-L1:在免疫细胞上表达100%,在肿瘤细胞上表达92%。首先,我们注意到肿瘤细胞PD-L1 +的百分比与高TIL百分比呈正相关(我们观察到,所有病例均显示出基质TIL,并以CD3 + / CD4 + T辅助细胞为主,从而支持了宫颈癌的强大免疫原性潜力。绝大多数肿瘤表达PD-L1:在免疫细胞上表达100%,在肿瘤细胞上表达92%。首先,我们注意到肿瘤细胞PD-L1 +的百分比与高TIL百分比呈正相关(p = 0.0073),并且在炎症细胞上的PD-L1表达增加(p = 0.0297)。其次,我们观察到TILs的百分比(p = 0.0105)与炎性细胞上PD-L1的表达(p = 0.01045)和对NACT的病理反应之间存在显着相关性。这些结果表明,子宫颈癌在新辅助治疗中也可能是免疫治疗的良好靶标。此外,PD-L1表达与基质TILs显着相关,有趣的是可能预测对NACT的病理反应。

更新日期:2020-09-11
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