TGF-β signaling suppresses tumor surveillance by converting conventional NK cells into ILC1s — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. TGF-β signaling suppresses tumor surveillance by converting conventional NK cells into ILC1s

TGF-β signaling suppresses tumor surveillance by converting conventional NK cells into ILC1s (#219)

Yulong Gao 1 2 , Fernando Guimaraes 1 3 , Tobias Bald 1 , Kyohei Nakamura 1 , Susanna Ng 4 , Arabella Young 1 2 , Shin Foong Ngiow 1 , Jai Rautela 3 , Meriem Messaoudene 5 , Nic Waddell 6 , Laurence Zitvogel 5 , Gabrielle Belz 3 , Christian Engwerda 4 , Nicholas Huntington 3 , Michael Hoelzel 7 , Mark Smyth 1 2
  1. Immunology in Cancer and Infection , QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  2. School of Medicine, The University of Queensland, Herston, QLD, Australia
  3. Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  4. Immunology and Infectoin, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  5. Gustave Roussy Cancer Campus, Villejuif, France
  6. Medical Genomics, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  7. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany

Avoiding destruction by immune cells is a hallmark of cancer, yet how cancer evade NK cell immunity remains incompletely understood. In this study, we describe the previously unrecognized TGF-β-dependent differentiation of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid cell (intILC1, CD49a+CD49b+Eomes+) and ILC1 (CD49a+CD49b-Eomes-) populations. In subcutaneous tumor models, we observed that tumor weight was positively correlated with intILC1 percentage, but was negatively correlated with NK cell percentage; while ILC1 population remained steady. Interestingly, closer examination revealed up-regulated checkpoint molecule expression (LAG-3, TIGIT and CTLA-4, etc.) and a lower IFN-γ/TNF-α production ratio in tumor intILC1s and ILC1s. Furthermore, in lymphopenic and tumor microenvironment, NK cells were able to differentiate into intILC1s and ILC1s, which process is largely dependent on TGF-β. By utilizing various transgenic mouse models, we showed that NK cells are crucial effector cells in cancer immunity, while the anti-tumor functions of intILC1s and ILC1s are impaired. Our findings highlight the unexpected plasticity of NK cells under pathophysiological conditions and reveal a novel mechanism by which tumors escape innate immune responses.

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