Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy

Abstract

<h3>Objectives:</h3> The association between the prognosis of advanced cervical cancer treated with cisplatin-based concurrent chemoradiotherapy (CCRT) and the number of tumor-infiltrating lymphocytes (TILs) in biopsy samples collected before treatment was examined, to (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intra-tumoral abundance of various specific TILs is a prognostic indicator in women with advanced cervical cancer who undergo treatment with CCRT, and (iii) investigate subtypes of FOXP3+ T cells in cervical cancer samples. <h3>Methods:</h3> In this retrospective study, intratumoral lesions in colpo-scopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT were analyzed. The informed consent was obtained from all patients, and approval to conduct this study was granted from the institutional review board. The International Federation of Gynecology and Obstetrics clinical stages of these patients were as follows: Stage IIA1 (n=8), Stage IIA2 (n=6), Stage IIb (n=32), Stage IIIa (n=1), and Stage IIIb (n=8). Biopsy samples were subjected to automatic immunological staining using the following six antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and clinicopathological characteristics or survial status were analyzed. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were stained with CD45RA antibody and investigated by flow cytometry. <h3>Results:</h3> Correlations between density of TILs and clinicopathological characteristics were examined. Only weak infiltration of CD8+ lymphocytes was found to be associated with PLN metastasis. No other factors were found to be associated with immune cell infiltration. Better survival was found to be associated with high densities of CD3+, CD4+, CD8+, CD206+, and FOXP3+ T cells, while there were no statistically significant associations with CD20+ B cell density. The subtypes of FOXP3+ TILs were analyzed in 15 fresh tumor samples, and non-Tregs (FOXP3lowCD45RA–) which have anti-tumor activity, were detected in all cases. <h3>Conclusions:</h3> The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.