Abstract

Objective To investigate the association between programmed death-ligand 1 (PD-L1) coupled with CD8+ tumor-infiltrating lymphocytes (TILS) and the clinicopathological features, along with prognosis of cervical squamous cell carcinoma (CSCC). Methods 95 patients of CSCC received tumor resection at the Department of Pathology of the First Affiliated Hospital of University of Science and Technology of China (USTC) from 2015 to 2020. Full-automatic immunohistochemistry was applied to measure PD-L1 expression and CD8+ TILS density. Our literature deeply assessed the links between PD-L1 expression, clinicopathological features, and the influences of combination of PD-L1 and CD8+ TILS (PD-L1+/CD8+ TILS) on the prognosis of CSCC. Results 64.21% of CSCC patients (61/95) expressed PD-L1, and PD-L1 expression was related to the Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, invasion depth, differentiation degree, metastasis of lymph node, and vascular invasion (P < 0.05). Dramatic correlation between PD-L1 expression and CD8+ TILS density was illustrated in CSCC patients (r = −0.461, P < 0.001). Obvious differences in differentiation degree, FIGO stage, infiltration depth, and lymph node metastasis were shown between patients with PD-L1 coupled with high-density of CD8+ TILS and those with PD-L1 coupled with low-density of CD8+ TILS (P < 0.05). Patients with PD-L1 negative expression exhibited better prognosis compared with those with PD-L1 positive expression (P < 0.05). Patients with PD-L1 coupled with high-density of CD8+ TILS showed better prognostic status, while those with PD-L1 coupled with low-density of CD8+ TILS had worse prognostic condition (P < 0.05). Differentiation, metastasis of lymph node, and FIGO stage were substantive impact elements of a CSCC patient's overall survival (OS) by Cox multivariate analysis. Conclusions CD8+ TILS density is related to PD-L1 expression in carcinoma. PD-L1/CD8+ TILS density can be regarded as evaluation for the prognosis of patients with CSCC, providing a new therapeutic target in clinical application.

Highlights

  • As one of the malignant carcinomas, cervical squamous cell carcinoma (CSCC) widely occurs in gynecology with a long incubation period. 569,847 of new cases worldwide and 311,365 of mortality was shown in the International Agency for Research on Cancer’s latest statistics [1]

  • Studies have found that programmed cell death-1 (PD-1) on tumor-infiltrating lymphocytes (TILS) can be combined with the programmed death ligand-1 (PD-L1) on tumor cells and inhibits T cell proliferation and activation

  • As classified by the International Federation of Gynecology and Obstetrics (FIGO) stage, 77 cases were from stage I to II and 18 cases were from stage III to IV. 66 cases retained a high level of differentiation, and 19 cases retained a low level of differentiation

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Summary

Introduction

As one of the malignant carcinomas, cervical squamous cell carcinoma (CSCC) widely occurs in gynecology with a long incubation period. 569,847 of new cases worldwide and 311,365 of mortality was shown in the International Agency for Research on Cancer’s latest statistics [1]. 569,847 of new cases worldwide and 311,365 of mortality was shown in the International Agency for Research on Cancer’s latest statistics [1]. Cervical cancer is mainly treated by surgery and radiotherapy, supplemented by chemotherapy. The development of new therapeutics targeting immune checkpoints has renewed interest in the use of immunotherapy in cervical cancer patients. Accompanied by new diagnostic techniques and treatment development, cervical cancer incidence in developed countries has decreased dramatically, but the mortality in developing countries still remains at a high level [2]. Multiple factors and genes were reported to be linked to cervical cancer occurrence and progression. During this process, the individual immune function was greatly affected. Studies have found that programmed cell death-1 (PD-1) on tumor-infiltrating lymphocytes (TILS) can be combined with the programmed death ligand-1 (PD-L1) on tumor cells and inhibits T cell proliferation and activation,

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