Single-cell profiling of acral melanoma infiltrating lymphocytes reveals a suppressive tumor microenvironment
Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM. Compared with cutaneous melanoma, ALM showed a lower frequency of tumor-reactive CD8 clusters and an enrichment of regulatory T cells with direct tumor recognition ability, suggesting a suppressive immune microenvironment in ALM. Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including <i>KLRC1</i> (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.
Authors
- Tomohide Tsukahara (ORCID: https://orcid.org/0000-0002-3678-4359)
- Yuka Mizue (ORCID: https://orcid.org/0000-0002-2208-0772)
- Kenta Sasaki (ORCID: https://orcid.org/0000-0001-8070-3045)
- Kohei Horimoto (ORCID: https://orcid.org/0000-0002-2682-7167)
- Tokimasa Hida (ORCID: https://orcid.org/0000-0003-3662-0095)
- Toshiya Handa (ORCID: https://orcid.org/0000-0002-0502-6037)
- Serina Tokita (ORCID: https://orcid.org/0009-0000-4256-5569)
- Kenji Murata (ORCID: https://orcid.org/0000-0002-2613-5144)
- Hisashi Uhara (ORCID: https://orcid.org/0000-0001-5391-3397)
- Aiko Murai (ORCID: https://orcid.org/0009-0007-9270-4521)
- Takayuki Kanaseki (ORCID: https://orcid.org/0000-0001-7294-6880)
- Junji Kato (ORCID: https://orcid.org/0000-0002-8734-445X)
- Tomoyuki Minowa
- Yoshihiko Hirohashi (ORCID: https://orcid.org/0000-0002-0608-3914)
- Terufumi Kubo (ORCID: https://orcid.org/0000-0001-9274-2551)
- Toshihiko Torigoe (ORCID: https://orcid.org/0000-0002-9463-5917)
- Sayuri Sato (ORCID: https://orcid.org/0000-0002-8961-3510)
- Munehide Nakatsugawa
Institutions
- Sapporo Medical University (JP)
- Tokyo Medical University Hachioji Medical Center (JP)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2024-12-04
- DOI
- https://doi.org/10.1126/scitranslmed.adk8832
- Citations
- 19
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 4.57