TIL Cell Therapy in HIV Positive Patient With Metastatic Melanoma: Case Report

Researchers at Northwestern University, with collaborators from the University of Chicago and McGaw Medical Center, have reported the first known case of tumor-infiltrating lymphocyte (TIL) therapy in a patient with well-controlled HIV and metastatic melanoma. This case report, published in Frontiers in Oncology, demonstrates that lifileucel-based TIL therapy can be feasibly administered in this historically excluded population, with manageable toxicity, temporary immune perturbation, and an early radiographic response.

TIL therapy has become an important later-line treatment for metastatic melanoma that progresses after immune checkpoint inhibitors, with lifileucel showing objective response rates above 30% in heavily pretreated patients. However, people living with HIV, even with virologically suppressed disease, have often been excluded from cellular therapy trials because of concerns around immune competence, viral rebound, lymphodepleting chemotherapy, and high-dose IL-2. In this case report, the authors describe a 37-year-old man with long-standing HIV on antiretroviral therapy and rapidly progressive, BRAF-V600E mutant metastatic melanoma with bulky axillary disease and pulmonary metastases despite pembrolizumab, ipilimumab/nivolumab, BRAF/MEK-targeted therapy with nivolumab, and attempted nivolumab/relatlimab. He underwent TIL harvest, lymphodepleting chemotherapy with cyclophosphamide and fludarabine, lifileucel infusion, and high-dose IL-2, while continuing HIV therapy.

TIL therapy was generally tolerated, consistent with expected treatment-related toxicities and without the patient’s HIV status causing complications. Although lymphodepletion led to marked immune suppression, the main acute toxicities were grade 1 cytokine release syndrome and IL-2–associated grade 3 hypotension. Importantly, HIV control was not durably disrupted: viral load rose transiently to 57.7 copies/mL on day +15 but returned to undetectable by day +22 and remained suppressed through day +100. The patient also had an early antitumor response, with day +44 imaging showing a partial response, including reduction of the axillary mass to 6.6 × 3.7 × 8.3 cm, decreased hilar lymphadenopathy to 0.8 cm, and smaller pulmonary nodules measuring up to 1.2 cm. However, this response was not durable, with progression by day +86 and death on day +358. Overall, the case suggests that TIL therapy may be feasible in carefully selected patients with controlled HIV, while reinforcing the need to include people living with HIV in prospective cellular therapy trials.

Reference:

Whetsell B, Alban J, Lin AY, Wayne JD, Chandra S. TIL cell therapy in HIV positive patient with metastatic melanoma: case report. Front Oncol. 2026;16:1818578. Published 2026 May 20. http:doi.org/10.3389/fonc.2026.1818578