Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator

Abstract

B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.

Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review

“…B7-H3 is an immune checkpoint protein and an important regulator of the adaptive immune response [98]. B7-H3 seems to be overexpressed in different HNC subtypes, and its high expression is an adverse prognostic factor for distant control and tumor-specific survival in HNC [99]. HNC PDX model (H score: 240) treated with MGC018 at 3 mg/kg (Q2W × 2) led to 98% reduction in tumor volume compared with vehicle-treated animals, while only 52% tumor reduction was detected in mice treated with control ADC at 3 mg/kg.…”