PMID- 35508657
OWN - NLM
STAT- MEDLINE
DCOM- 20220520
LR  - 20240119
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 605
IP  - 7910
DP  - 2022 May
TI  - Landscape of helper and regulatory antitumour CD4(+) T cells in melanoma.
PG  - 532-538
LID - 10.1038/s41586-022-04682-5 [doi]
AB  - 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 molecules(1,2), 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 (T(Reg)) cells could 
      be indirectly elicited through presentation of tumour antigens via 
      antigen-presenting cells. Notably, numerous tumour-reactive CD4(+) T(Reg) 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(+) T(Reg) cells as a mechanism of 
      immune evasion that is favoured in HLA class II-positive melanoma.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Oliveira, Giacomo
AU  - Oliveira G
AUID- ORCID: 0000-0001-7435-5603
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 
      giacomo_oliveira@dfci.harvard.edu.
AD  - Harvard Medical School, Boston, MA, USA. giacomo_oliveira@dfci.harvard.edu.
FAU - Stromhaug, Kari
AU  - Stromhaug K
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Cieri, Nicoletta
AU  - Cieri N
AUID- ORCID: 0000-0003-1340-6272
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Iorgulescu, J Bryan
AU  - Iorgulescu JB
AUID- ORCID: 0000-0003-1405-3667
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Klaeger, Susan
AU  - Klaeger S
AUID- ORCID: 0000-0002-0074-5163
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Wolff, Jacquelyn O
AU  - Wolff JO
AD  - Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Rachimi, Suzanna
AU  - Rachimi S
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Chea, Vipheaviny
AU  - Chea V
AUID- ORCID: 0000-0002-6592-8710
AD  - Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, 
      MA, USA.
FAU - Krause, Kate
AU  - Krause K
AD  - Department of surgery, Massachusetts General Hospital, Boston, MA, USA.
FAU - Freeman, Samuel S
AU  - Freeman SS
AUID- ORCID: 0000-0001-8285-0057
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Zhang, Wandi
AU  - Zhang W
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Li, Shuqiang
AU  - Li S
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, 
      MA, USA.
FAU - Braun, David A
AU  - Braun DA
AUID- ORCID: 0000-0003-4543-5553
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of 
      Medicine, New Haven, CT, USA.
FAU - Neuberg, Donna
AU  - Neuberg D
AUID- ORCID: 0000-0003-2566-3145
AD  - Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Carr, Steven A
AU  - Carr SA
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Livak, Kenneth J
AU  - Livak KJ
AUID- ORCID: 0000-0001-9105-5856
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, 
      MA, USA.
FAU - Frederick, Dennie T
AU  - Frederick DT
AUID- ORCID: 0000-0003-3355-5267
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
FAU - Fritsch, Edward F
AU  - Fritsch EF
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Wind-Rotolo, Megan
AU  - Wind-Rotolo M
AD  - Bristol-Myers Squibb, Cambridge, MA, USA.
FAU - Hacohen, Nir
AU  - Hacohen N
AUID- ORCID: 0000-0002-2349-2656
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
FAU - Sade-Feldman, Moshe
AU  - Sade-Feldman M
AUID- ORCID: 0000-0002-0022-0287
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
FAU - Yoon, Charles H
AU  - Yoon CH
AUID- ORCID: 0000-0003-1231-3840
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Division of Surgical Oncology, Brigham and Women's Hospital Boston, Boston, MA, 
      USA.
FAU - Keskin, Derin B
AU  - Keskin DB
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, 
      MA, USA.
AD  - Department of Computer Science, Metropolitan College, Boston University, Boston, 
      MA, USA.
AD  - Department of Health Technology, Technical University of Denmark, Lyngby, 
      Denmark.
FAU - Ott, Patrick A
AU  - Ott PA
AUID- ORCID: 0000-0002-4253-943X
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Rodig, Scott J
AU  - Rodig SJ
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Boland, Genevieve M
AU  - Boland GM
AD  - Harvard Medical School, Boston, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Department of surgery, Massachusetts General Hospital, Boston, MA, USA.
FAU - Wu, Catherine J
AU  - Wu CJ
AUID- ORCID: 0000-0002-3348-5054
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 
      cwu@partners.org.
AD  - Harvard Medical School, Boston, MA, USA. cwu@partners.org.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA. cwu@partners.org.
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. 
      cwu@partners.org.
LA  - eng
GR  - P50 CA240243/CA/NCI NIH HHS/United States
GR  - P01 CA229092/CA/NCI NIH HHS/United States
GR  - T32 CA079443/CA/NCI NIH HHS/United States
GR  - P50 CA101942/CA/NCI NIH HHS/United States
GR  - U24 CA224331/CA/NCI NIH HHS/United States
GR  - U19 AI082630/AI/NIAID NIH HHS/United States
GR  - R21 CA216772/CA/NCI NIH HHS/United States
GR  - R01 CA155010/CA/NCI NIH HHS/United States
GR  - R01 CA229261/CA/NCI NIH HHS/United States
GR  - T32 HG002295/HG/NHGRI NIH HHS/United States
GR  - K12 CA090354/CA/NCI NIH HHS/United States
GR  - R01 CA208756/CA/NCI NIH HHS/United States
GR  - R50 CA251956/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20220504
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA Antigens)
SB  - IM
CIN - Signal Transduct Target Ther. 2023 Jan 16;8(1):34. PMID: 36646683
MH  - Antigen-Presenting Cells
MH  - *Antigens, Neoplasm/immunology
MH  - *CD4-Positive T-Lymphocytes
MH  - HLA Antigens
MH  - Humans
MH  - *Melanoma/immunology
MH  - Phenotype
MH  - *Skin Neoplasms/immunology
MH  - Tumor Cells, Cultured
MH  - Tumor Microenvironment
PMC - PMC9815755
MID - NIHMS1861468
EDAT- 2022/05/05 06:00
MHDA- 2022/05/21 06:00
PMCR- 2023/01/05
CRDT- 2022/05/04 23:49
PHST- 2021/07/23 00:00 [received]
PHST- 2022/03/23 00:00 [accepted]
PHST- 2022/05/05 06:00 [pubmed]
PHST- 2022/05/21 06:00 [medline]
PHST- 2022/05/04 23:49 [entrez]
PHST- 2023/01/05 00:00 [pmc-release]
AID - 10.1038/s41586-022-04682-5 [pii]
AID - 10.1038/s41586-022-04682-5 [doi]
PST - ppublish
SO  - Nature. 2022 May;605(7910):532-538. doi: 10.1038/s41586-022-04682-5. Epub 2022 
      May 4.