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

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Abstract

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.

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All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Authors and Affiliations

  1. Department of Radiological, Oncological, and Pathological Sciences, Sapienza University - Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy

    Nicoletta D’Alessandris & Irene Pecorella

  2. Department of Maternal and Child Health and Urological Sciences, Sapienza University - Policlinico Umberto I, Rome, Italy

    Innocenza Palaia, Federica Tomao, Anna Di Pinto, Lucia Musacchio & Pierluigi Benedetti Panici

  3. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University – Polo Pontino, Latin, Italy

    Angelina Pernazza, Martina Leopizzi, Valeria Di Maio & Carlo Della Rocca

Authors
  1. Nicoletta D’Alessandris
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  2. Innocenza Palaia
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  3. Angelina Pernazza
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  4. Federica Tomao
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  5. Anna Di Pinto
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  6. Lucia Musacchio
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  9. Irene Pecorella
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  10. Pierluigi Benedetti Panici
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  11. Carlo Della Rocca
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Contributions

D’Alessandris Nicoletta and Pernazza Angelina carried out the pathologic analysis and manuscript writing; Palaia Innocenza and Di Pinto Anna collected and critically analyzed clinical data; Tomao Federica contributed to statistical analysis; Musacchio Lucia collected clinical data; Leopizzi Martina and Di Maio Valeria performed statistical analysis; Pecorella Irene contributed to the pathological analysis; Benedetti Panici Pierluigi revised the work; Della Rocca Carlo contributed to the analysis of the pathologic findings, revised, and edited the work for important intellectual content.

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Correspondence to Nicoletta D’Alessandris.

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The study complies with ethical standards of our Institution. All patients gave their informed consent.

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D’Alessandris, N., Palaia, I., Pernazza, A. et al. PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer. Virchows Arch 478, 517–525 (2021). https://doi.org/10.1007/s00428-020-02922-5

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  • DOI: https://doi.org/10.1007/s00428-020-02922-5

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