Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans.

Autor:	Ludin A; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA.; These authors contributed equally., Stirtz GL; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; These authors contributed equally., Tal A; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Nirmal AJ; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Ludwig Center at Harvard; Boston, MA, USA.; Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Systems Biology, Harvard Medical School; Boston, MA, USA., Besson N; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Jones SM; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Pfaff KL; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Manos M; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Liu S; Biophysics Program, Harvard University, Boston, MA 02115, USA.; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Barrera I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Gong Q; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Rodrigues CP; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA., Sahu A; Dermatology Service, Memorial Sloan Kettering Cancer Center; New York, NY, USA.|., Jerison E; Department of Physics, University of Chicago, Chicago, IL 60637, USA, Institute for Biophysical Dynamics, and James Franck Institute., Alessi JV; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Ricciuti B; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Richardson DS; Harvard Center for Biological Imaging, Department of Molecular and Cellular Biology, Harvard University; Cambridge, MA, USA., Weiss JD; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Moreau HM; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Stanhope ME; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Afeyan AB; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Sefton J; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., McCall WD; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Formato E; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA., Yang S; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA., Zhou Y; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA., van Konijnenburg DPH; Division of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Cole HL; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA., Cordova M; Dermatology Service, Memorial Sloan Kettering Cancer Center; New York, NY, USA.|., Deng L; Dermatology Service, Memorial Sloan Kettering Cancer Center; New York, NY, USA.|., Rajadhyaksha M; Dermatology Service, Memorial Sloan Kettering Cancer Center; New York, NY, USA.|., Quake SR; Department of Bioengineering and Applied sciences, Stanford University, Stanford, CA, USA.; Chan Zuckerberg Biohub, San Francisco, CA, USA., Awad MM; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Chen F; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sorger PK; Ludwig Center at Harvard; Boston, MA, USA.; Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA.; Department of Systems Biology, Harvard Medical School; Boston, MA, USA., Hodi FS; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215.; Parker Institute for Cancer Immunotherapy., Rodig SJ; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Murphy GF; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Zon LI; Harvard Stem Cell and Regenerative Biology Department, Harvard University; Boston, MA, USA.; Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute; Boston, MA, USA.; Howard Hughes Medical Institute, Harvard medical school; Boston MA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 19. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1101/2024.09.18.613595
Abstrakt:	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. Competing Interests: L.I.Z. is a founder and stockholder of Fate Therapeutics, CAMP4 Therapeutics, Amagma Therapeutics, Scholar Rock, and Branch Biosciences. He is a consultant for Celularity and Cellarity. JVA is on the BMS and AstraZeneca advisory board and a consultrant for MSD, Janssen. F.S.H reports grants and personal fees from Bristol-Myers Squibb, personal fees from Merck, grants and personal fees from Novartis, personal fees from Surface, personal fees from Compass Therapeutics, personal fees from Apricity, personal fees from 7 Hills Pharma, personal fees from Bicara, personal fees from Checkpoint Therapeutics, personal fees from Bioentre, personal fees from Gossamer, personal fees from Iovance, personal fees from Catalym, personal fees from Immunocore, personal fees from Kairos, personal fees from Rheos, personal fees from Zumutor, personal fees from Corner Therapeuitcs, personal fees from Puretech, personal fees from Curis, personal fees from Astra Zeneca, personal fees from Solu Therapeutics, outside the submitted work; In addition, Dr. Hodi has a patent Methods for Treating MICA-Related Disorders (#20100111973) with royalties paid, a patent Tumor antigens and uses thereof (#7250291) issued, a patent Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603) pending, a patent Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407) pending, a patent Therapeutic peptides (#20160046716) pending, a patent Therapeutic Peptides (#20140004112) pending, a patent Therapeutic Peptides (#20170022275) pending, a patent Therapeutic Peptides (#20170008962) pending, a patent THERAPEUTIC PEPTIDES Ðherapeutic PeptidesÐatent number: 9402905 issued, a patent METHODS OF USING PEMBROLIZUMAB AND TREBANANIB pending, a patent Vaccine compositions and methods for restoring NKG2D pathway function against cancers Ðatent number: 10279021 issued, a patent Úntibodies that bind to MHC class I polypeptide-related Sequence A Ð’dÐatent number: 10106611 issued, a patent ÚNTI-GALECTIN ANTIBODY BIOMARKERS PREDICTIVE OF ANTI-IMMUNE CHECKPOINT AND ANTI-ANGIOGENESIS RESPONSES Ð’dÐublication number: 20170343552 pending, and a patent Antibodies against EDIL3 and methods of use thereof pending. JVA: Advisory board: BMS, AstraZeneca Consultant: MSD, Janssen.
Databáze:	MEDLINE
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