The Steroidal Profile Modulates Adaptive Immune Response and Prognosis in Adrenocortical Carcinoma: Analysis of TCR and BCR Repertoires.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignant neoplasm with limited therapeutic options and an often poor prognosis. A deeper understanding of its interaction with the immune system is essential for the advancement of personalized treatment strategies, particularly in light of the tumor heterogeneity of hormone production. ACC tumors can be classified into high steroid phenotype (HSP) and low steroid phenotype (LSP) subtypes, which exhibit distinct biological behaviors and immunological microenvironments. However, the composition and prognostic significance of T-cell and B-cell receptor (TCR and BCR) repertoires in these subtypes remain largely unknown. In this study, we demonstrate that steroid phenotype is a key determinant of the adaptive immune response and clinical outcomes in ACC. LSP tumors exhibit significantly higher lymphocytic infiltration and greater repertoire diversity, reflecting a more immunogenic tumor microenvironment, despite the significant expression of immune evasion and exhaustion genes. These findings provide new insights into how the hormonal environment shapes the immunobiology of ACC, reveal possible mechanisms of immune escape in cortisol-producing tumors, and highlight the prognostic relevance of immune repertoire characteristics. Our results support the integration of TCR/BCR profiling with steroid phenotyping to improve risk stratification and inform the design of precision immunotherapeutic strategies for ACC.