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Tumor-Infiltrating Clonal Hematopoiesis

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Title: Tumor-Infiltrating Clonal Hematopoiesis
Authors: Oriol Pich, Elsa Bernard, Maria Zagorulya, Andrew Rowan, Constandina Pospori, Ramy Slama, Hector Huerga Encabo, Jennifer O’Sullivan, Despoina Papazoglou, Panayiotis Anastasiou, Chrysante S. Iliakis, Sally-Ann Clark, Krijn K. Dijkstra, Vittorio Barbè, Chris Bailey, Aaron J. Stonestrom, Katey S.S. Enfield, Mary Green, Charlotte K. Brierley, Alastair Magness, David R. Pearce, Robert E. Hynds, Rija Zaidi, Jayant K. Rane, Ángel F. Álvarez-Prado, Kerstin Thol, Rachel Scott, Supreet Kaur Bola, Elena Hoxha, Steve K. Harris, Karl S. Peggs, Sergio A. Quezada, Allan Hackshaw, Simone Zaccaria, Johanna A. Joyce, Ilaria Malanchi, Michael F. Berger, Mariam Jamal-Hanjani, Andreas Wack, Julian Downward, William Grey, Cristina Lo Celso, Eva Grönroos, Charles M. Rudin, Adam J. Mead, Dominique Bonnet, Elli Papaemmanuil, Charles Swanton
Source: N Engl J Med
The New England journal of medicine, vol. 392, no. 16, pp. 1594-1608
Publisher Information: Massachusetts Medical Society, 2025.
Publication Year: 2025
Subject Terms: Male, Lung Neoplasms, Middle Aged, Article, Monocytes, Dioxygenases, DNA-Binding Proteins, Mice, Observational Studies as Topic, Cell Movement, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Mutation, Tumor Microenvironment, Animals, Humans, Female, Prospective Studies, Clonal Hematopoiesis, Neoplasm Recurrence, Local, Aged, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/immunology, Carcinoma, Non-Small-Cell Lung/mortality, Carcinoma, Non-Small-Cell Lung/pathology, Clonal Hematopoiesis/genetics, Clonal Hematopoiesis/immunology, Dioxygenases/genetics, DNA-Binding Proteins/genetics, Lung Neoplasms/genetics, Lung Neoplasms/mortality, Lung Neoplasms/pathology, Neoplasm Recurrence, Local/epidemiology, Neoplasm Recurrence, Local/genetics, Neoplasm Recurrence, Local/pathology, Tumor Microenvironment/immunology, Monocytes/immunology, Monocytes/pathology, Cell Movement/genetics, Cell Movement/immunology, Neoplasm Transplantation
Description: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). The frequency of TI-CH and its effect on tumor evolution are unclear.We characterized CHIP and TI-CH in 421 patients with early-stage non-small-cell lung cancer (NSCLC) from the TRACERx study and in 49,351 patients from the MSK-IMPACT pan-cancer cohort. We studied the association of TI-CH with survival and disease recurrence and evaluated the functional effect of TET2-mutant CHIP on the biologic features of lung tumors.Among patients with NSCLC, 42% of those with CHIP had TI-CH. TI-CH independently predicted an increased risk of death or recurrence, with an adjusted hazard ratio of 1.80 (95% confidence interval [CI], 1.23 to 2.63) as compared with the absence of CHIP and an adjusted hazard ratio of 1.62 (95% CI, 1.02 to 2.56) as compared with CHIP in the absence of TI-CH. Among patients with solid tumors, 26% of those with CHIP had TI-CH. TI-CH conferred a risk of death from any cause that was 1.17 times (95% CI, 1.06 to 1.29) as high as the risk with CHIP in the absence of TI-CH. TET2 mutations were the strongest genetic predictor of TI-CH; such mutations enhanced monocyte migration to lung tumor cells, fueled a myeloid-rich tumor microenvironment in mice, and resulted in the promotion of tumor organoid growth.TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution. (Funded by the Royal Society and others.).
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1533-4406
0028-4793
DOI: 10.1056/nejmoa2413361
Access URL: https://pubmed.ncbi.nlm.nih.gov/40267425
https://ora.ox.ac.uk/objects/uuid:e20d5bce-3d87-4ac2-9e89-b887ca4cc72b
https://doi.org/10.1056/nejmoa2413361
https://serval.unil.ch/notice/serval:BIB_435B0ABCF518
https://serval.unil.ch/resource/serval:BIB_435B0ABCF518.P001/REF.pdf
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_435B0ABCF5187
Rights: CC BY
URL: http://www.nejmgroup.org/legal/terms-of-use.htm
URL: http://creativecommons.org/licenses/by/4.0/This Author Accepted Manuscript is licensed for use under the CC-BY license.
Accession Number: edsair.doi.dedup.....0c02eadfc5172cb499191803751f35e5
Database: OpenAIRE
Description
Abstract:Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). The frequency of TI-CH and its effect on tumor evolution are unclear.We characterized CHIP and TI-CH in 421 patients with early-stage non-small-cell lung cancer (NSCLC) from the TRACERx study and in 49,351 patients from the MSK-IMPACT pan-cancer cohort. We studied the association of TI-CH with survival and disease recurrence and evaluated the functional effect of TET2-mutant CHIP on the biologic features of lung tumors.Among patients with NSCLC, 42% of those with CHIP had TI-CH. TI-CH independently predicted an increased risk of death or recurrence, with an adjusted hazard ratio of 1.80 (95% confidence interval [CI], 1.23 to 2.63) as compared with the absence of CHIP and an adjusted hazard ratio of 1.62 (95% CI, 1.02 to 2.56) as compared with CHIP in the absence of TI-CH. Among patients with solid tumors, 26% of those with CHIP had TI-CH. TI-CH conferred a risk of death from any cause that was 1.17 times (95% CI, 1.06 to 1.29) as high as the risk with CHIP in the absence of TI-CH. TET2 mutations were the strongest genetic predictor of TI-CH; such mutations enhanced monocyte migration to lung tumor cells, fueled a myeloid-rich tumor microenvironment in mice, and resulted in the promotion of tumor organoid growth.TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution. (Funded by the Royal Society and others.).
ISSN:15334406
00284793
DOI:10.1056/nejmoa2413361