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Updated: Jun 12, 2026
Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model
Published on: November 26, 2010
Adoptive Cell Transfer of Tumor-Infiltrating Lymphocytes for Metastatic Acral Lentiginous Melanoma
Paul H McClelland1, Shirley K Nah1, Alexandra M Gustafson1
1Surgery Branch, National Cancer Institute, Bethesda, MD.
Purpose:
Acral lentiginous melanoma is a subtype of cutaneous melanoma arising from palmar, plantar, or subungual skin. These tumors are characterized by aggressive biology, a low tumor mutational burden (TMB), and diminished sensitivity to immune checkpoint blockade. It is unknown whether adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) has efficacy in patients with acral melanoma.
Methods:
We analyzed prospectively collected data from 442 patients with metastatic cutaneous melanoma who were treated on clinical trials of ACT-TIL at a single institution between 1999 and 2018. Although blinded to treatment outcome and genomic data, we retrospectively identified patients who had acral subtype on the basis of clinicopathologic data available at the time of diagnosis. We then evaluated the ACT-TIL treatment outcomes of patients with acral melanoma and compared them with contemporaneously treated patients with nonacral melanoma.
Results:
Out of 442 included patients, 30 (7%) had acral melanoma while 412 (93%) had nonacral melanoma. Cohorts had similar clinical characteristics, protocol enrollment, and treatment-related factors. The objective response rate to ACT-TIL in patients with acral and nonacral melanomas was 43% and 40%, respectively (P = .87), with 3% and 16% having complete responses (CRs; P = .07). Median progression-free survival was 3.5 and 4.1 months (P = .40) and median overall survival was 13 and 17 months (P = .79), respectively. Acral melanomas had lower TMB and ultraviolet mutational signature scores than nonacral melanomas.
Conclusion:
ACT-TIL can mediate objective responses in patients with metastatic acral melanoma, and outcomes in patients with acral disease were unexpectedly comparable with those of contemporaneously treated patients with nonacral cutaneous melanoma. Further research is necessary to understand the immunologic basis of responses to ACT-TIL in acral melanoma and to increase the frequency of CRs.
Insights
Adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) shows comparable efficacy in acral melanoma patients versus nonacral melanoma. This study suggests ACT-TIL is a viable treatment option for acral melanoma, despite its aggressive nature.
Area of Science:
- Oncology
- Immunotherapy
- Dermatology
Background:
- Acral lentiginous melanoma (ALM) is a rare subtype of cutaneous melanoma.
- ALM is characterized by aggressive biology, low tumor mutational burden (TMB), and resistance to immune checkpoint blockade.
- The efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) in ALM remains unexplored.
Purpose of the Study:
- To evaluate the efficacy of ACT-TIL in patients with metastatic acral melanoma.
- To compare treatment outcomes of acral melanoma patients receiving ACT-TIL with those of nonacral melanoma patients.
Main Methods:
- Analysis of prospectively collected data from 442 metastatic cutaneous melanoma patients treated with ACT-TIL.
- Retrospective identification of 30 acral melanoma patients based on clinicopathologic data.
- Comparison of ACT-TIL treatment outcomes between acral and nonacral melanoma cohorts.
Main Results:
- Objective response rates to ACT-TIL were similar: 43% for acral melanoma vs. 40% for nonacral melanoma.
- Median progression-free survival (3.5 vs. 4.1 months) and overall survival (13 vs. 17 months) were comparable between groups.
- Acral melanomas exhibited lower TMB and ultraviolet mutational signatures compared to nonacral melanomas.
Conclusions:
- ACT-TIL can induce objective responses in metastatic acral melanoma patients.
- Treatment outcomes for acral melanoma patients receiving ACT-TIL were unexpectedly similar to those with nonacral melanoma.
- Further research is needed to elucidate the immunologic mechanisms of ACT-TIL response in acral melanoma and improve complete response rates.
