{"doi":"10.1101/2024.09.18.613595","title":"Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans","abstract":"Summary Immunotherapy leads to cancer eradication despite the tumor’s immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules. The craters harbor the highest density of CD8 + T cells in the tumor. In zebrafish, CD8 + T cells formed prolonged interactions with melanoma cells within craters, characteristic of antigen recognition. Following immunostimulatory treatment, the craters enlarged and became the major site of activated CD8 + T cell accumulation and tumor killing that was B2M dependent. In humans, craters predicted immune response to ICB therapy, showing response better than high T cell infiltration. This marks craters as potential new diagnostic tool for immunotherapy success and targets to enhance ICB response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491859,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1337762,"name":"Georgia L. Stirtz","orcid":null,"position":1,"is_corresponding":false},{"id":1337763,"name":"Asaf Tal","orcid":null,"position":2,"is_corresponding":false},{"id":621265,"name":"Ajit J. Nirmal","orcid":"0000-0003-4139-0618","position":3,"is_corresponding":false},{"id":1040517,"name":"N. Besson","orcid":"0009-0008-3548-913X","position":4,"is_corresponding":false},{"id":68220,"name":"Stephanie M. Jones","orcid":"0000-0003-4697-3169","position":5,"is_corresponding":false},{"id":38313,"name":"Kathleen L. Pfaff","orcid":"0000-0003-3311-5384","position":6,"is_corresponding":false},{"id":49571,"name":"Michael P. 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Cole","orcid":"0000-0002-3023-8998","position":27,"is_corresponding":false},{"id":366930,"name":"Miguel Córdova","orcid":"0000-0002-2962-0671","position":28,"is_corresponding":false},{"id":573544,"name":"Liang Deng","orcid":"0000-0002-8467-9342","position":29,"is_corresponding":false},{"id":366933,"name":"Milind Rajadhyaksha","orcid":"0000-0002-6323-4547","position":30,"is_corresponding":false},{"id":11049,"name":"Stephen R. Quake","orcid":"0000-0002-1613-0809","position":31,"is_corresponding":false},{"id":227614,"name":"Mark M. Awad","orcid":"0000-0003-0928-5244","position":32,"is_corresponding":false},{"id":24055,"name":"Fei Chen","orcid":"0000-0003-2308-3649","position":33,"is_corresponding":false},{"id":24147,"name":"Peter K. Sorger","orcid":"0000-0002-3364-1838","position":34,"is_corresponding":false},{"id":4541,"name":"F. Stephen Hodi","orcid":"0000-0001-6825-091X","position":35,"is_corresponding":false},{"id":3736,"name":"Scott J. 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