PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell
Nicoletta D'Alessandris1, Innocenza Palaia2, Angelina Pernazza3
1Department of Radiological, Oncological, and Pathological Sciences, Sapienza University - Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy. ndalessandris@gmail.com.
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.
Insights
Cervical cancer shows strong immune potential, with high PD-L1 expression on tumor and immune cells. Tumor-infiltrating lymphocytes and PD-L1 levels may predict response to neoadjuvant chemotherapy, suggesting immunotherapy potential.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Cervical cancer remains a significant global health challenge, particularly in the neoadjuvant setting.
- Limited data exists on the role of immune checkpoint inhibitors in cervical cancer management.
- Understanding the tumor microenvironment is crucial for developing effective immunotherapies.
Purpose of the Study:
- To investigate the presence and characteristics of tumor-infiltrating lymphocytes (TILs) in cervical cancer.
- To evaluate programmed death-ligand 1 (PD-L1) expression in the tumor microenvironment.
- To determine the association between TILs, PD-L1 expression, and pathological response to neoadjuvant chemotherapy (NACT).
Main Methods:
- Analysis of 38 squamous cell cervical cancer patients undergoing NACT and surgery.
- Immunohistochemical evaluation of TILs (T cells, B cells, macrophages, etc.) and PD-L1 expression.
- Correlation of TILs and PD-L1 levels with pathological response to NACT.
Main Results:
- All tumors exhibited stromal TILs, predominantly CD4+ T helper cells, indicating immunogenic potential.
- High PD-L1 expression was observed on both immune cells (100%) and tumor cells (92%).
- Neoplastic PD-L1 positivity correlated with higher TIL percentage and PD-L1 on inflammatory cells.
- TIL percentage and PD-L1 expression on inflammatory cells significantly correlated with pathological response to NACT.
Conclusions:
- Cervical cancer demonstrates significant immunogenic potential, making it a promising candidate for immunotherapy.
- PD-L1 expression and TILs are associated with pathological response to NACT in cervical cancer.
- These findings support the exploration of immunotherapy in the neoadjuvant treatment of cervical cancer.
