Tumor-Infiltrating Clonal Hematopoiesis
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, C. Donovan Bailey, Aaron J. Stonestrom, Katey S.S. Enfield, Mary Green, Charlotte 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 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
Abstract
BACKGROUND: 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. METHODS: -mutant CHIP on the biologic features of lung tumors. RESULTS: 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. CONCLUSIONS: 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.).