PMID- 36054337
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20221007
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 7
IP  - 75
DP  - 2022 Sep 2
TI  - Autoreactive napsin A-specific T cells are enriched in lung tumors and 
      inflammatory lung lesions during immune checkpoint blockade.
PG  - eabn9644
LID - 10.1126/sciimmunol.abn9644 [doi]
AB  - Cancer treatment with immune checkpoint blockade (ICB) often induces 
      immune-related adverse events (irAEs). We hypothesized that proteins coexpressed 
      in tumors and normal cells could be antigenic targets in irAEs and herein 
      described DITAS (discovery of tumor-associated self-antigens) for their 
      identification. DITAS computed transcriptional similarity between lung tumors and 
      healthy lung tissue based on single-sample gene set enrichment analysis. This 
      identified 10 lung tissue-specific genes highly expressed in the lung tumors. 
      Computational analysis was combined with functional T cell assays and single-cell 
      RNA sequencing of the antigen-specific T cells to validate the lung tumor 
      self-antigens. In patients with non-small cell lung cancer (NSCLC) treated with 
      ICB, napsin A was a self-antigen that elicited strong CD8(+) T cell responses, 
      with ICB responders harboring higher frequencies of these CD8(+) T cells compared 
      with nonresponders. Human leukocyte antigen (HLA) class I ligands derived from 
      napsin A were present in human lung tumors and in nontumor lung tissues, and 
      napsin A tetramers confirmed the presence of napsin A-specific CD8(+) T cells in 
      blood and tumors of patients with NSCLC. Napsin A-specific T cell clonotypes were 
      enriched in lung tumors and ICB-induced inflammatory lung lesions and could kill 
      immortalized HLA-matched NSCLC cells ex vivo. Single-cell RNA sequencing revealed 
      that these T cell clonotypes expressed proinflammatory cytokines and cytotoxic 
      markers. Thus, DITAS successfully identified self-antigens, including napsin A, 
      that likely mediate effective antitumor T cell responses in NSCLC and may 
      simultaneously underpin lung irAEs.
FAU - Berner, Fiamma
AU  - Berner F
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Bomze, David
AU  - Bomze D
AUID- ORCID: 0000-0003-2958-7055
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
FAU - Lichtensteiger, Christa
AU  - Lichtensteiger C
AUID- ORCID: 0000-0002-9478-0639
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Walter, Vincent
AU  - Walter V
AD  - Department of Dermatology, University Hospital Tubingen, University of Tubingen, 
      Tubingen, Germany.
FAU - Niederer, Rebekka
AU  - Niederer R
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Hasan Ali, Omar
AU  - Hasan Ali O
AUID- ORCID: 0000-0001-5185-7520
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Medical Genetics, Life Sciences Institute, University of British 
      Columbia, Vancouver, British Columbia, Canada.
AD  - Department of Dermatology, University Hospital Zurich, University of Zurich, 
      Zurich, Switzerland.
FAU - Wyss, Nina
AU  - Wyss N
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Bauer, Jens
AU  - Bauer J
AUID- ORCID: 0000-0003-3731-2385
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
FAU - Freudenmann, Lena Katharina
AU  - Freudenmann LK
AUID- ORCID: 0000-0002-9827-4979
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
AD  - German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner 
      Site Tubingen, Tubingen, Germany.
FAU - Marcu, Ana
AU  - Marcu A
AUID- ORCID: 0000-0003-0808-8097
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
FAU - Wolfschmitt, Eva-Maria
AU  - Wolfschmitt EM
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
FAU - Haen, Sebastian
AU  - Haen S
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
FAU - Gross, Thorben
AU  - Gross T
AUID- ORCID: 0000-0002-7907-4373
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
FAU - Abdou, Marie-Therese
AU  - Abdou MT
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Diem, Stefan
AU  - Diem S
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Knopfli, Stella
AU  - Knopfli S
AUID- ORCID: 0000-0003-4016-4256
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Sinnberg, Tobias
AU  - Sinnberg T
AD  - Department of Dermatology, University Hospital Tubingen, University of Tubingen, 
      Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
FAU - Hofmeister, Kathrin
AU  - Hofmeister K
AUID- ORCID: 0000-0002-4121-9215
AD  - Department of Dermatology, University Hospital Tubingen, University of Tubingen, 
      Tubingen, Germany.
FAU - Cheng, Hung-Wei
AU  - Cheng HW
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Toma, Marieta
AU  - Toma M
AD  - Institute of Pathology, University Hospital Bonn (UKB), University of Bonn, Bonn, 
      Germany.
FAU - Klumper, Niklas
AU  - Klumper N
AD  - Department of Urology, University Hospital Bonn (UKB), University of Bonn, Bonn, 
      Germany.
AD  - Institute of Experimental Oncology, University Hospital Bonn (UKB), University of 
      Bonn, Bonn, Germany.
FAU - Purde, Mette-Triin
AU  - Purde MT
AUID- ORCID: 0000-0002-2631-9736
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Pop, Oltin Tiberiu
AU  - Pop OT
AUID- ORCID: 0000-0001-8000-2310
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Jochum, Ann-Kristin
AU  - Jochum AK
AUID- ORCID: 0000-0002-6981-1384
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Pascolo, Steve
AU  - Pascolo S
AD  - Department of Dermatology, University Hospital Zurich, University of Zurich, 
      Zurich, Switzerland.
FAU - Joerger, Markus
AU  - Joerger M
AUID- ORCID: 0000-0001-6602-6287
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Fruh, Martin
AU  - Fruh M
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
AD  - Department of Oncology, University of Bern, Bern, Switzerland.
FAU - Jochum, Wolfram
AU  - Jochum W
AUID- ORCID: 0000-0001-6170-2020
AD  - Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Rammensee, Hans-Georg
AU  - Rammensee HG
AUID- ORCID: 0000-0003-1614-2647
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner 
      Site Tubingen, Tubingen, Germany.
FAU - Laubli, Heinz
AU  - Laubli H
AUID- ORCID: 0000-0002-8910-5620
AD  - Division of Oncology, University Hospital Basel, University of Basel, Basel, 
      Switzerland.
FAU - Holzel, Michael
AU  - Holzel M
AUID- ORCID: 0000-0003-4048-8824
AD  - Institute of Experimental Oncology, University Hospital Bonn (UKB), University of 
      Bonn, Bonn, Germany.
FAU - Neefjes, Jacques
AU  - Neefjes J
AUID- ORCID: 0000-0001-6763-2211
AD  - Department of Cell and Chemical Biology, Oncode Institute, Leiden University 
      Medical Center, Netherlands.
FAU - Walz, Juliane
AU  - Walz J
AUID- ORCID: 0000-0001-6404-7391
AD  - Clinical Collaboration Unit Translational Immunology, German Cancer Consortium 
      (DKTK), Department of Internal Medicine, University Hospital Tubingen, Tubingen, 
      Germany.
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
AD  - Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed 
      Tumor Therapies", University of Tubingen, Tubingen, Germany.
AD  - German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner 
      Site Tubingen, Tubingen, Germany.
AD  - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and Robert Bosch 
      Center for Tumor Diseases (RBCT), Stuttgart, Germany.
FAU - Flatz, Lukas
AU  - Flatz L
AUID- ORCID: 0000-0001-9683-8390
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Dermatology, University Hospital Tubingen, University of Tubingen, 
      Tubingen, Germany.
AD  - Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Dermatology, University Hospital Zurich, University of Zurich, 
      Zurich, Switzerland.
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220902
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Autoantigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Antigens, Neoplasm
MH  - Autoantigens
MH  - CD8-Positive T-Lymphocytes
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - Histocompatibility Antigens Class I
MH  - Humans
MH  - Immune Checkpoint Inhibitors
MH  - Lung
MH  - *Lung Neoplasms/genetics
EDAT- 2022/09/03 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/09/02 14:03
PHST- 2022/09/02 14:03 [entrez]
PHST- 2022/09/03 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
AID - 10.1126/sciimmunol.abn9644 [doi]
PST - ppublish
SO  - Sci Immunol. 2022 Sep 2;7(75):eabn9644. doi: 10.1126/sciimmunol.abn9644. Epub 
      2022 Sep 2.