Dissecting response to neoadjuvant immunotherapy-treated melanoma using cancer-immunity cycle-associated signatures
Abstract Neoadjuvant combination therapy with anti-PD-1 and anti-CTLA4 agents has significantly improved long-term survival in patients with metastatic melanoma, yet not all patients respond to treatment. Responders often exhibit upregulated baseline inflammatory signatures; however, these markers c...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-06-01
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| Series: | Cancer Immunology, Immunotherapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00262-025-04094-0 |
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| Summary: | Abstract Neoadjuvant combination therapy with anti-PD-1 and anti-CTLA4 agents has significantly improved long-term survival in patients with metastatic melanoma, yet not all patients respond to treatment. Responders often exhibit upregulated baseline inflammatory signatures; however, these markers capture only a single facet of the Cancer-Immunity Cycle—a comprehensive model describing the sequential steps required for effective anti-cancer immunity. To determine whether non-responsiveness to immunotherapy arises from single or multiple ‘defective’ steps, we analyzed in melanoma patients, treated with neoadjuvant immunotherapy, gene signatures representing each step of the cycle. Patients not achieving a major pathological response showed overall lower expression of these signatures. Among the ‘immune-hot’ patients, we identified a low response subgroup defective in one step (‘homing-to-the-tumor,’ involving CXCL9 and CXCL10), making this a promising target for improving their outcomes. |
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| ISSN: | 1432-0851 |