Prognostic Relevance of Tumor-Infiltrating Immune Cells in Cervix Squamous Cell Carcinoma

SIMPLE SUMMARY: Although tumor immune infiltration has been analyzed in a variety of tumor entities, it has never been investigated in cervical cancer in relation to histological subtypes and prognosis. Therefore, the aim of this study was to investigate the prognostic impact of tumor immune infiltration in a panel of 238 sporadic cervical cancer cases by quantifying the levels of tumor-infiltrating immune cells (TIICs) and correlate them with the histological subtype and with patient survival. The level of TIIC was significantly enhanced in cervix squamous cell carcinomas (CSCC) versus cervix adenocarcinomas (CAC) and represented an independent positive prognosticator for disease-free survival (DFS) in patients with CSCC. ABSTRACT: There exists a variety of studies about tumor-infiltrating immune cells (TIICs) in cervical cancer, but their prognostic value in correlation with the histopathological subtype has never been investigated. Therefore, the aim of this study was to quantify TIICs in a panel of 238 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIICs levels were significantly increased in the subgroup of CSCC (191 samples) in comparison to CAC (47 samples). In CSCC, TIICs’ infiltration showed a negative correlation with age, FIGO stage and with the histone protein modification H3K4me3. Moreover, in CAC, it was positively correlated with p16 and with the glucocorticoid receptor and inversely correlated with the MDM2 protein and with H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease-free survival (DFS) in patients with CSCC, those bearing tumors with the strongest TIICs infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIIC levels and prognosis in patients with CSCC vs. patients with CAC.