Positive TIGIT and VISTA Expression Predict Worse Prognosis in Cervical Cancer Patients Treated with (Chemo)Radiotherapy

Abstract

Immune checkpoint inhibitors combined with (chemo)radiotherapy could be an attractive treatment strategy for patients with cervical cancer (CC), but the expression of some immune checkpoint proteins in cervical cancer and their impact on patient survival remains largely unknown. Here, we investigated the predictive value of T cell immunoreceptor with Ig and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and lymphocyte-activation gene-3 (LAG-3) expression in pathological tissues of CC patients treated with (chemo)radiotherapy. We enrolled 175 CC patients who received (chemo)radiotherapy and collected their pre-treatment tumor tissue sections for the immunohistochemical stain of TIGIT, VISTA, and LAG-3. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) after (chemo)radiotherapy. Univariate and multivariate COX proportional hazards regression models were employed to analyze potential risk factors for patient survival. Kaplan-Meier survival analyses showed that the PFS and OS of patients with positive expression of TIGIT and VISTA were significantly shorter than those patients with negative expression of the proteins (all p<0.05). However, we did not reach the same conclusion in the analysis of LAG-3 (both p>0.05). Univariate COX regression analysis showed that the positive expression of TIGIT and VISTA are related to poor PFS and OS (both HR>1.0 and p<0.05). Multivariate COX regression analysis showed that TIGIT positive and VISTA positive patients have shorter PFS and OS (both HR>1.0 and p<0.05). There is no significant correlation between LAG-3 expression and PFS or OS in these CC patients treated with (chemo)radiotherapy. We revealed that positive TIGIT and VISTA expression could predict worse prognosis in cervical cancer patients treated with (chemo)radiotherapy, which may help to refine the treatment strategies of combining immune checkpoint inhibitors and radiotherapy.