Table 1.
Mechanisms of resistance in renal cell carcinoma
| Mechanisms of resistance | Main components involved in resistance | Major trials addressing resistance to ICI |
| Tumor microenvironment | CD8+ T-cells | JAVELIN RENAL 101 exploratory analysis[50], NCT03013335 |
| T-regulatory cells | ||
| Myeloid-derived suppressor cells | ||
| Tumor-associated macrophages | NCT03013335 | |
| Memory T-cells | ||
| Cytokines | ||
| Oncogenic pathways | IFN-γ signaling | NCT03010176 |
| MAPK pathway | ||
| Wnt/β-catenin pathway | ||
| Immune checkpoints | PD-1 | TITAN-RCC, TiNivo-2 (NCT04987203) |
| PD-L1 | CONTACT-03 | |
| CTLA-4 | NCT03849469, TITAN-RCC | |
| TIM3 | NCT03652077, NCT02608268 | |
| LAG3 | NCT02996110, NCT02996110, NCT03849469, NCT00351949 | |
| BTLA | ||
| TIGIT | NCT03119428 | |
| Other factors | Hypoxia |
NCT03634540, NCT04195750, NCT03634540 |
| Gut microbiome | NCT03829111, GETUG-AFU 26 NIVOREN multicenter phase II study[79] |
BTLA: B and T lymphocyte attenuator; CTLA-4: cytotoxic T lymphocyte-associated protein 4; ICI: immune checkpoint inhibitor; IFN-γ: interferon-γ; LAG3: lymphocyte-activation gene 3; MAPK: mitogen-activated protein kinase; PD-1: programmed death-1; PD-L1: programmed death ligand-1; RCC: renal cell carcinoma; TIGIT: T cell immunoglobulin and ITIM domain; TIM3: T cell immunoglobulin and mucin domain 3.