| Autor: |
Minowa, Tomoyuki, Murata, Kenji, Mizue, Yuka, Murai, Aiko, Nakatsugawa, Munehide, Sasaki, Kenta, Tokita, Serina, Kubo, Terufumi, Kanaseki, Takayuki, Tsukahara, Tomohide, Handa, Toshiya, Sato, Sayuri, Horimoto, Kohei, Kato, Junji, Hida, Tokimasa, Hirohashi, Yoshihiko, Uhara, Hisashi, Torigoe, Toshihiko |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 12/4/2024, Vol. 16 Issue 776, p1-17, 17p |
| Abstrakt: |
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 KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM. Editor's summary: Unlike cutaneous melanoma, immune checkpoint therapies have not proven successful for acral lentiginous melanoma (ALM). Here, Minowa et al. profiled ALM samples to determine why. They found that, unlike cutaneous melanoma, ALM tumors had reduced effector T cell infiltration and increased regulatory T cell abundance. Moreover, the effector T cells in the tumor expressed coinhibitory markers. Targeting one coinhibitory marker, NKG2A, restored function to T cells in vitro, particularly in combination with PD-1 blockade, suggesting that combination immunotherapies may benefit patients with ALM. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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