多次自体 TIL（肿瘤浸润淋巴细胞）(LM103 输注) 治疗联合免疫检查点抑制剂在侵袭性黏膜黑色素瘤患者中诱导反复肿瘤消退：病例报告及文献综述

Tumor-infiltrating lymphocyte (TIL) therapy was approved as a one-dose treatment indicated for melanoma patients who have progressed on anti-PD-1 therapy.

However, the majority of patients show only short-duration responses, highlighting the urgent need to explore multiple cycles of TIL therapy and combination strategies.

We report a case of a patient with aggressive stage IV nasal mucosal malignant melanoma with disease progression on multiple lines of immunotherapy who was enrolled in a clinical trial evaluating the safety and efficacy of autologous TIL therapy. Prior to TIL infusion, the patient underwent lymphodepletion with cyclophosphamide followed by fludarabine for 5 days.

Approximately 24 hours later, the patient received an intravenous infusion of autologous TIL, followed by high-dose interleukin-2 for 6 days to support T-cell expansion and persistence. The patient achieved a partial response (PR) at 6 weeks and a complete response (CR) at 12 weeks post-infusion.

However, tumor relapse occurred 7 months later. The patient then received a second TIL infusion, resulting in stable disease (SD) with transient shrinkage, but rapid regrowth occurred within 3 weeks. The patient subsequently received a third TIL infusion and achieved another PR within 2 weeks. Manageable adverse events were observed and resolved shortly after TIL treatments. A time-course study of peripheral blood cell subtyping and cytokine secretion demonstrated a long-term immune response.

Longitudinal immune monitoring revealed sustained systemic immune activation. This case report shows that multiple autologous TIL therapies can induce repeated clinical and immunological responses in a heavily anti-PD-1-pretreated patient with advanced melanoma, underscoring the feasibility and therapeutic potential of multiple TIL treatments. Clinical trial registration: https://clinicaltrials. gov, identifier NCT06697665, NCT05941936, NCT05971589.