Efficacy and safety of immune checkpoint inhibitors in young adults with metastatic melanoma

Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma

“…These results suggest the potential to reshape the immune TME with additional immune augmentation, such as combination or alternative ICI therapies. Similar to a previous study on young adult melanoma 12 , we observed that AYA patients treated with combination ICI therapy had a higher response rate and longer PFS than monotherapy, which may be associated with T reg enrichment in the TME. These findings support the use of combination therapy as a potential strategy to overcome T reg -mediated immunosuppression and improve treatment outcomes in AYA melanoma patients.…”

“…This may lead to lower immune recognition and hence reduced ICI efficacy. Other studies found similar mutational burdens between AYA and adults 12 , 18 . We observed a higher frequency of somatic mutations in BRAF , but not PTEN , in AYA patients compared to adults, and the AYA mutational profiles were not distinctly associated with TME profiles or ICI-resistance.…”

“…The same study observed higher immunosuppressive regulatory:cytotoxic T cell ratios in patients <60 years old, with regulatory T cell (T reg ) depletion leading to increased response to anti-PD-1 in younger mice. More recently, a retrospective study compared young adult melanoma patients ≤40 years to older age groups, and found no overall difference in immunotherapy response based on age, but young adults had a significantly higher response rate (53% vs 38%) and improved PFS (median 13.7 vs 4.0 months) with combination ICI (anti-PD-1+anti-CTLA-4) compared to monotherapy 12 . The same study also analyzed patients ≤30 years, which also showed better or trends towards better outcomes with combination ICI vs anti-PD-1 monotherapy (objective response rates of 57% vs 44%, PFS 13.8 vs 4.0 months, OS 82.1 vs 24.1 months) 12 .…”