Author
Listed:
- Giacomo Oliveira
(Dana-Farber Cancer Institute
Harvard Medical School)
- Kari Stromhaug
(Dana-Farber Cancer Institute)
- Nicoletta Cieri
(Dana-Farber Cancer Institute)
- J. Bryan Iorgulescu
(Dana-Farber Cancer Institute
Harvard Medical School
Brigham and Women’s Hospital)
- Susan Klaeger
(Broad Institute of MIT and Harvard)
- Jacquelyn O. Wolff
(Center for Immuno-Oncology, Dana-Farber Cancer Institute)
- Suzanna Rachimi
(Broad Institute of MIT and Harvard)
- Vipheaviny Chea
(Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute)
- Kate Krause
(Massachusetts General Hospital)
- Samuel S. Freeman
(Harvard Medical School
Broad Institute of MIT and Harvard)
- Wandi Zhang
(Dana-Farber Cancer Institute)
- Shuqiang Li
(Broad Institute of MIT and Harvard
Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute)
- David A. Braun
(Dana-Farber Cancer Institute
Harvard Medical School
Broad Institute of MIT and Harvard
Yale Cancer Center, Yale School of Medicine)
- Donna Neuberg
(Dana-Farber Cancer Institute)
- Steven A. Carr
(Broad Institute of MIT and Harvard)
- Kenneth J. Livak
(Dana-Farber Cancer Institute
Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute)
- Dennie T. Frederick
(Broad Institute of MIT and Harvard
Massachusetts General Hospital)
- Edward F. Fritsch
(Dana-Farber Cancer Institute
Broad Institute of MIT and Harvard)
- Megan Wind-Rotolo
(Bristol-Myers Squibb)
- Nir Hacohen
(Harvard Medical School
Broad Institute of MIT and Harvard
Massachusetts General Hospital)
- Moshe Sade-Feldman
(Broad Institute of MIT and Harvard
Massachusetts General Hospital)
- Charles H. Yoon
(Dana-Farber Cancer Institute
Brigham and Women’s Hospital Boston)
- Derin B. Keskin
(Dana-Farber Cancer Institute
Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute
Boston University
Technical University of Denmark)
- Patrick A. Ott
(Dana-Farber Cancer Institute
Harvard Medical School
Broad Institute of MIT and Harvard
Brigham and Women’s Hospital)
- Scott J. Rodig
(Brigham and Women’s Hospital
Brigham and Women’s Hospital)
- Genevieve M. Boland
(Harvard Medical School
Broad Institute of MIT and Harvard
Massachusetts General Hospital)
- Catherine J. Wu
(Dana-Farber Cancer Institute
Harvard Medical School
Broad Institute of MIT and Harvard
Brigham and Women’s Hospital)
Abstract
Within the tumour microenvironment, CD4+ T cells can promote or suppress antitumour responses through the recognition of antigens presented by human leukocyte antigen (HLA) class II molecules1,2, but how cancers co-opt these physiologic processes to achieve immune evasion remains incompletely understood. Here we performed in-depth analysis of the phenotype and tumour specificity of CD4+ T cells infiltrating human melanoma specimens, finding that exhausted cytotoxic CD4+ T cells could be directly induced by melanoma cells through recognition of HLA class II-restricted neoantigens, and also HLA class I-restricted tumour-associated antigens. CD4+ T regulatory (TReg) cells could be indirectly elicited through presentation of tumour antigens via antigen-presenting cells. Notably, numerous tumour-reactive CD4+ TReg clones were stimulated directly by HLA class II-positive melanoma and demonstrated specificity for melanoma neoantigens. This phenomenon was observed in the presence of an extremely high tumour neoantigen load, which we confirmed to be associated with HLA class II positivity through the analysis of 116 melanoma specimens. Our data reveal the landscape of infiltrating CD4+ T cells in melanoma and point to the presentation of HLA class II-restricted neoantigens and direct engagement of immunosuppressive CD4+ TReg cells as a mechanism of immune evasion that is favoured in HLA class II-positive melanoma.
Suggested Citation
Giacomo Oliveira & Kari Stromhaug & Nicoletta Cieri & J. Bryan Iorgulescu & Susan Klaeger & Jacquelyn O. Wolff & Suzanna Rachimi & Vipheaviny Chea & Kate Krause & Samuel S. Freeman & Wandi Zhang & Shu, 2022.
"Landscape of helper and regulatory antitumour CD4+ T cells in melanoma,"
Nature, Nature, vol. 605(7910), pages 532-538, May.
Handle:
RePEc:nat:nature:v:605:y:2022:i:7910:d:10.1038_s41586-022-04682-5
DOI: 10.1038/s41586-022-04682-5
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Livius Penter & Mehdi Borji & Adi Nagler & Haoxiang Lyu & Wesley S. Lu & Nicoletta Cieri & Katie Maurer & Giacomo Oliveira & Aziz M. Al’Khafaji & Kiran V. Garimella & Shuqiang Li & Donna S. Neuberg & , 2024.
"Integrative genotyping of cancer and immune phenotypes by long-read sequencing,"
Nature Communications, Nature, vol. 15(1), pages 1-18, December.
- Georges Bedran & Daniel A. Polasky & Yi Hsiao & Fengchao Yu & Felipe Veiga Leprevost & Javier A. Alfaro & Marcin Cieslik & Alexey I. Nesvizhskii, 2023.
"Unraveling the glycosylated immunopeptidome with HLA-Glyco,"
Nature Communications, Nature, vol. 14(1), pages 1-12, December.
- Denise Lau & Sonal Khare & Michelle M. Stein & Prerna Jain & Yinjie Gao & Aicha BenTaieb & Tim A. Rand & Ameen A. Salahudeen & Aly A. Khan, 2022.
"Integration of tumor extrinsic and intrinsic features associates with immunotherapy response in non-small cell lung cancer,"
Nature Communications, Nature, vol. 13(1), pages 1-12, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:605:y:2022:i:7910:d:10.1038_s41586-022-04682-5. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.