Abstract

Introduction Renal cell carcinomas (RCC) are resistant to chemotherapy and radiotherapy, and effective treatment options remain limited. Immunotherapy has emerged as a promising approach, and circular RNAs (circRNAs) are increasingly recognized as key regulators of tumor immunity. This study aims to elucidate the regulatory relationship between circPVT1 and antitumor immunosuppression in RCC. Methods CircPVT1 expression and its prognostic value were analyzed in RCC samples. The effects of circPVT1 knockdown on RCC cell proliferation, invasion, and metastasis were examined in vitro . Singlecell sequencing was used to assess macrophage infiltration in circPVT1high versus circPVT1low groups. ELISA was performed to measure secretion of IL4, IL10, and TGFβ by tumor cells. In addition, nanotherapeutic system delivering circPVT1 inhibitors was tested for its antitumor efficacy. Results CircPVT1 was highly expressed in RCC and correlated with poor prognosis. Knockdown of circPVT1 significantly suppressed cell proliferation, invasion, and metastasis. Singlecell sequencing revealed increased macrophage infiltration in the circPVT1high group. ELISA results demonstrated that circPVT1 knockdown reduced tumor cell secretion of IL4, IL10, and TGFβ, thereby promoting macrophage polarization toward the M1 phenotype. Mechanistically, circPVT1 promoted RCC progression by regulating EMT. Furthermore, a nanotherapeutic system containing circPVT1 inhibitors effectively inhibited RCC growth. Discussion These findings indicate that circPVT1 plays a critical role in RCC immune evasion by modulating macrophage polarization and EMT. Therefore, circPVT1 may be a predictor of ccRCC immune evasion and a potential therapeutic target.