LAG3 and cancer: In addition, circulating biomarkers, including peripheral blood T-cell receptor (TCR) clonality and early changes incirculating tumor DNA (ctDNA), are under investigation as minimally invasive surrogates for tumor response and emerging resistance.Mechanisms of resistance encompass loss of antigen presentation through β2-microglobulin mutations, upregulation of alternateinhibitory receptors (e.g., TIM-3, LAG-3), and establishment of an immunosuppressive stromal barrier via regulatory Tcells, myeloid-derived suppressor cells, and cancer-associated fibroblasts.