PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer

• Published in: Virchows Archiv : an international journal of pathology 2021-03, Vol.478 (3), p.517-525
• Main Authors: D’Alessandris, Nicoletta, Palaia, Innocenza, Pernazza, Angelina, Tomao, Federica, Di Pinto, Anna, Musacchio, Lucia, Leopizzi, Martina, Di Maio, Valeria, Pecorella, Irene, Benedetti Panici, Pierluigi, Della Rocca, Carlo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; B7-H1 Antigen - analysis; Biomarkers, Tumor - analysis; Cancer; Cancer immunotherapy; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; CD3 antigen; CD4 antigen; CD8 antigen; Cervical cancer; Cervix; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - therapeutic use; Clinical Decision-Making; Cytotoxicity; Databases, Factual; Eosinophils; Female; Helper cells; Humans; Hysterectomy; Immune checkpoint; Immune system; Immunogenicity; Immunohistochemistry; Immunophenotyping; Immunotherapy; Inflammation; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Macrophages; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Neoplasia; Neoplasms; Original Article; Paclitaxel - therapeutic use; Pathology; PD-L1 protein; Platinum; Population studies; Predictive Value of Tests; Retrospective Studies; Surgery; Treatment Outcome; Tumor cells; Tumor Microenvironment; Tumor-infiltrating lymphocytes; Tumors; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-020-02922-5

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.