CD4 <sup>+</sup> T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses-Reference-Cited by-同舟云学术

CD4 ⁺ T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses

Published:2024-01-19 Issue:91 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Bawden Emma G.¹²^ORCID,Wagner Teagan¹^ORCID,Schröder Jan³^ORCID,Effern Maike¹²^ORCID,Hinze Daniel²,Newland Lewis¹²^ORCID,Attrill Grace H.⁴⁵⁶^ORCID,Lee Ariane R.¹^ORCID,Engel Sven¹^ORCID,Freestone David¹^ORCID,de Lima Moreira Marcela¹^ORCID,Gressier Elise¹^ORCID,McBain Nathan¹^ORCID,Bachem Annabell¹^ORCID,Haque Ashraful¹^ORCID,Dong Ruining³⁷^ORCID,Ferguson Angela L.⁵⁶⁸⁹^ORCID,Edwards Jarem J.⁴⁵⁶,Ferguson Peter M.⁴⁵¹⁰¹¹^ORCID,Scolyer Richard A.⁴⁵⁶¹⁰¹¹^ORCID,Wilmott James S.⁴⁵⁶^ORCID,Jewell Christopher M.¹²¹³¹⁴¹⁵^ORCID,Brooks Andrew G.¹^ORCID,Gyorki David E.¹⁶¹⁷,Palendira Umaimainthan⁴⁵⁶^ORCID,Bedoui Sammy¹,Waithman Jason¹⁸¹⁹^ORCID,Hochheiser Katharina¹¹⁷^ORCID,Hölzel Michael²^ORCID,Gebhardt Thomas¹^ORCID

Affiliation:

1. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

2. Institute of Experimental Oncology (IEO), Medical Faculty, University Hospital Bonn, University of Bonn, Bonn 53105, Germany.

3. Computational Sciences Initiative, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.

4. Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia.

5. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

6. Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.

7. Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.

8. Centenary Institute, University of Sydney, Sydney, NSW, Australia.

9. Infection, Immunity and Inflammation theme, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.

10. Department of Tissue Oncology and Diagnostic Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

11. NSW Health Pathology, Sydney, NSW, Australia.

12. Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.

13. United States Department of Veterans Affairs, VA Maryland Health Care System, Baltimore, MD, USA.

14. Robert E. Fischell Institute for Biomedical Devices, College Park, MD, USA.

15. Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, USA.

16. Division of Cancer Surgery, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

17. Peter MacCallum Cancer Centre Melbourne, Melbourne, VIC, Australia.

18. Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.

19. School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Abstract

Whereas CD4 + T cells conventionally mediate antitumor immunity by providing help to CD8 + T cells, recent clinical studies have implied an important role for cytotoxic CD4 + T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4 + T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4 + T cells with tumor debris-laden MHC II + host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II + melanoma cells alone could also promote CD4 + T cell control. CD4 + T cells stably suppressed or eradicated tumors even in the absence of other lymphocytes by using tumor necrosis factor–α and Fas ligand (FasL) but not perforin-mediated cytotoxicity. Interferon-γ was critical for protection, acting both directly on melanoma cells and via induction of nitric oxide synthase in myeloid cells. Our results illustrate multifaceted and context-specific aspects of MHC II–dependent CD4 + T cell immunity against cutaneous melanoma, emphasizing modulation of this axis as a potential avenue for immunotherapies.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine,Immunology

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.adi9517

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