Association between Tumor Mutational Burden, Stromal CD8(+) Tumor-Infiltrating Lymphocytes, and Clinical Factors in Cervical Cancers Treated with Radiotherapy

SIMPLE SUMMARY: We retrospectively analyzed the association between tumor mutational burden (TMB) and/or the density of stromal CD8-positive tumor-infiltrating lymphocytes (CD8(+)TILs) and clinical factors in 44 patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy. We found that (i) TMB was not associated with CD8(+)TIL density; (ii) TMB-high plus CD8(+)TIL density-low status predicted a worse prognosis than either of the two factors alone; and (iii) TMB-high or CD8(+)TIL density-high status was associated with the presence of ARID1A mutations. These data suggest no association between TMB and CD8(+)TIL density, but involvement of ARID1A mutations, in antitumor immune responses in patients with cervical cancers treated with radiotherapy. ABSTRACT: Background: Tumor mutational burden (TMB) and stromal CD8-positive tumor-infiltrating lymphocytes (CD8(+)TILs) serve important roles in antitumor immune responses to radiotherapy. This study aimed to elucidate the association between TMB, CD8(+)TILs, and clinical factors in patients with cervical cancer treated with radiotherapy. Methods: Patients with squamous cell carcinoma of the uterine cervix treated with definitive radiotherapy, and with available somatic mutation data and immunohistochemical staining data from identical tumor tissues, were enrolled retrospectively. The association between TMB and/or CD8(+)TIL density and patient characteristics, mutation profiles, and treatment outcome was analyzed. Results: The study analyzed 44 patients (median follow-up period, 61 months). There was no significant correlation between TMB and CD8(+)TIL density, or between TMB or CD8(+)TIL density and patient characteristics. TMB-high or CD8(+)TIL density-low status was associated with worse overall survival and distant metastasis-free survival; the predictive value of these factors became greater when used in combination. TMB-high or CD8(+)TIL density-high status was associated with ARID1A mutations. Conclusions: These data indicate independence of TMB and CD8(+)TIL density and the involvement of ARID1A alterations in antitumor immune responses in patients with cervical cancers treated with radiotherapy, warranting further mechanistic research and prospective validation.