Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer

Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.

We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.

Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z = - 8.635, p < 0.001) and peritumoral (median 113.53 vs. 82.48; Z = - 3.741, p < 0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z = - 0.817,p = 0.414) and peritumoral (median 402.56 vs. 390.84; Z = - 1.138,p = 0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z = - 2.009, p = 0.045) and peritumoral areas(median 63.31 vs. 98.48; Z = - 2.469, p = 0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR = 0.297; 95% CI, 0.109-0.810, p = 0.018) and overall survival (HR = 0.078; 95% CI, 0.010-0.598, p = 0.014).

NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.