HAVCR2 and neoplasm: Clinically, some patients exhibit primary resistance, possibly due to a highly iTME or a low tumor mutational burden.[26, 27] Moreover, even in initially responsive tumors, acquired resistance can develop via alternative immune escape pathways such as TIM‐3 and LAG‐3.[28, 29, 30, 31, 32] Tumor heterogeneity further complicates treatment, as spatially variable PD‐L1 expression within tumors may impair therapeutic efficacy.[33, 34] In addition, systemically administered PD‐L1 antibodies often suffer from poor targeting specificity, leading to rapid clearance by the RES.