Respon Imun Adaptif pada Kanker Ginjal: Implikasi terhadap Patogenesis, Biomarker, dan Imunoterapi

Abstract

Latar Belakang: Karsinoma sel ginjal (renal cell carcinoma/RCC), terutama clear cell RCC (ccRCC), merupakan keganasan urologi yang imunogenik dan memiliki insidens yang terus meningkat. Immune checkpoint inhibitor (ICI) telah mengubah tata laksana RCC stadium lanjut, tetapi resistensi primer maupun didapat masih menjadi kendala. Tinjauan ini membahas peran respons imun adaptif, biomarker prediktif, dan implikasinya terhadap imunoterapi RCC.

Metode: Tinjauan literatur naratif dilakukan terhadap publikasi tahun 2021–2025 dari basis data biomedis utama, dilengkapi studi landmark sebelumnya. Topik meliputi tumor microenvironment (TME), exhaustion sel T, populasi imun regulator, biomarker, dan luaran uji klinis.

Hasil: Respons imun adaptif pada RCC terutama dimediasi limfosit T CD8+ sitotoksik, tetapi paparan antigen kronik menyebabkan exhaustion sel T dan penurunan fungsi efektor. Subpopulasi progenitor exhausted T cell (Tpex; PD-1+TCF1+) berperan penting terhadap respons ICI. Sel T regulator mendukung imunosupresi melalui IL-10, TGF-β, dan CTLA-4, sedangkan sel B serta tertiary lymphoid structures (TLS) berpotensi menjadi prediktor positif respons terapi. Biomarker yang relevan mencakup densitas dan komposisi TIL, rasio CD8+/Treg, ekspresi PD-L1, tanda tangan transkriptomik, dan keberadaan TLS. Regimen nivolumab, nivolumab–ipilimumab, pembrolizumab–axitinib, dan nivolumab–cabozantinib telah menunjukkan manfaat klinis bermakna.

Simpulan: Imunitas adaptif berperan sentral dalam patogenesis dan respons terapi RCC. Integrasi biomarker imun multimodal diperlukan untuk mendukung pemilihan regimen dual ICI atau kombinasi ICI–TKI secara lebih presisi.

Background: Renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC), is an immunogenic urologic malignancy with a steadily increasing incidence. Immune checkpoint inhibitors (ICIs) have transformed the management of advanced RCC, although primary and acquired resistance remain major challenges. This review summarizes the role of adaptive immunity, predictive biomarkers, and their therapeutic implications in RCC.

Methods: A narrative review was conducted using publications from 2021–2025 identified through major biomedical databases, supplemented by earlier landmark studies. The review focused on the tumor microenvironment (TME), T-cell exhaustion, regulatory immune populations, biomarkers, and clinical trial outcomes.

Results: Adaptive immune responses in RCC are primarily mediated by cytotoxic CD8+ T lymphocytes; however, chronic antigen exposure induces T-cell exhaustion and progressive loss of effector function. Progenitor exhausted T cells (Tpex; PD-1+TCF1+) are important mediators of responsiveness to ICIs. Regulatory T cells promote immunosuppression through IL-10, TGF-β, and CTLA-4, whereas B cells and tertiary lymphoid structures (TLS) may serve as positive predictors of treatment response. Relevant biomarkers include tumor-infiltrating lymphocyte density and composition, the CD8+/Treg ratio, PD-L1 expression, transcriptomic immune signatures, and TLS presence. Nivolumab, nivolumab–ipilimumab, pembrolizumab–axitinib, and nivolumab–cabozantinib have demonstrated meaningful clinical benefit.

Conclusion: Adaptive immunity is central to RCC pathogenesis and therapeutic response. Integrating multimodal immune biomarkers may support more precise selection between dual-ICI and ICI–TKI regimens.