PMID- 34858733
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Print)
IS  - 2162-4011 (Linking)
VI  - 10
IP  - 1
DP  - 2021
TI  - Keratinocyte differentiation antigen-specific T cells in immune checkpoint 
      inhibitor-treated NSCLC patients are associated with improved survival.
PG  - 2006893
LID - 10.1080/2162402X.2021.2006893 [doi]
LID - 2006893
AB  - Immune checkpoint inhibitors (ICIs) have improved the survival of patients with 
      non-small cell lung cancer (NSCLC) by reinvigorating tumor-specific T cell 
      responses. However, the specificity of such T cells and the human leukocyte 
      antigen (HLA)-associated epitopes recognized, remain elusive. In this study, we 
      identified NSCLC T cell epitopes of recently described NSCLC-associated antigens, 
      termed keratinocyte differentiation antigens. Epitopes of these antigens were 
      presented by HLA-A 03:01 and HLA-C 04:01 and were associated with responses to 
      ICI therapy. Patients with CD8(+) T cell responses to these epitopes had improved 
      overall and progression-free survival. T cells specific for such epitopes could 
      eliminate HLA class I-matched NSCLC cells ex vivo and were enriched in patient 
      lung tumors. The identification of novel lung cancer HLA-associated epitopes that 
      correlate with improved ICI-dependent treatment outcomes suggests that 
      keratinocyte-specific proteins are important tumor-associated antigens in NSCLC. 
      These findings improve our understanding of the mechanisms of ICI therapy and may 
      help support the development of vaccination strategies to improve ICI-based 
      treatment of these tumors.
CI  - (c) 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Berner, Fiamma
AU  - Berner F
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
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 - Luimstra, Jolien J
AU  - Luimstra JJ
AD  - Department of Cell and Chemical Biology, Oncode Institute, Leiden University 
      Medical Center, Leiden, The Netherlands.
AD  - Oncode Institute, Utrecht, The Netherlands.
FAU - Pop, Oltin Tiberiu
AU  - Pop OT
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Jochum, Ann-Kristin
AU  - Jochum AK
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Purde, Mette-Triin
AU  - Purde MT
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Hasan Ali, Omar
AU  - Hasan Ali O
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Medical Genetics, Life Sciences Institute, University of British 
      Columbia, Vancouver, Canada.
AD  - Department of Dermatology, University Hospital Zurich, University of Zurich, 
      Zurich, Switzerland.
FAU - Bomze, David
AU  - Bomze D
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
FAU - Bauer, Jens
AU  - Bauer J
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
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
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
AD  - Interfaculty Institute for Cell Biology, Department of Immunology, University of 
      Tubingen, Tubingen, Germany.
FAU - Dubbelaar, Marissa Lisa
AU  - Dubbelaar ML
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), 
      Quantitative Biology Center (QBiC), University of Tubingen, Tubingen, Germany.
FAU - Abdou, Marie-Therese
AU  - Abdou MT
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Baumgaertner, Petra
AU  - Baumgaertner P
AUID- ORCID: 0000-0002-5979-7654
AD  - Department of Oncology, Ludwig Cancer Research, University of Lausanne, 
      Switzerland.
FAU - Appenzeller, Christina
AU  - Appenzeller C
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Cicin-Sain, Caroline
AU  - Cicin-Sain C
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Lenz, Tobias
AU  - Lenz T
AD  - Research Unit Evolutionary Immunogenomics, Department of Biology, University of 
      Hamburg, Hamburg, Germany.
FAU - Speiser, Daniel E
AU  - Speiser DE
AUID- ORCID: 0000-0003-2031-3250
AD  - Department of Oncology, Ludwig Cancer Research, University of Lausanne, 
      Switzerland.
FAU - Ludewig, Burkhard
AU  - Ludewig B
AUID- ORCID: 0000-0002-7685-573X
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Driessen, Christoph
AU  - Driessen C
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, 
      Switzerland.
FAU - Jorger, Markus
AU  - Jorger M
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
AD  - Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
AD  - Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Cozzio, Antonio
AU  - Cozzio A
AD  - Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
FAU - Rammensee, Hans-Georg
AU  - Rammensee HG
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 - Walz, Juliane
AU  - Walz J
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.
AD  - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and Robert Bosch 
      Center for Tumor Diseases (RBCT), Stuttgart, Germany.
FAU - Neefjes, Jacques
AU  - Neefjes J
AD  - Department of Cell and Chemical Biology, Oncode Institute, Leiden University 
      Medical Center, Leiden, The Netherlands.
AD  - Oncode Institute, Utrecht, The Netherlands.
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, 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.
AD  - Department of Dermatology, University Hospital Tubingen, Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211127
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Antigens, Differentiation/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Humans
MH  - Immune Checkpoint Inhibitors
MH  - Keratinocytes
MH  - *Lung Neoplasms/drug therapy
PMC - PMC8632109
OTO - NOTNLM
OT  - Immune checkpoint inhibitor therapy
OT  - NSCLC
OT  - autoimmune toxicity
OT  - tumor-associated antigen
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/12/04 06:00
MHDA- 2022/01/04 06:00
PMCR- 2021/11/27
CRDT- 2021/12/03 07:06
PHST- 2021/12/03 07:06 [entrez]
PHST- 2021/12/04 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2021/11/27 00:00 [pmc-release]
AID - 2006893 [pii]
AID - 10.1080/2162402X.2021.2006893 [doi]
PST - epublish
SO  - Oncoimmunology. 2021 Nov 27;10(1):2006893. doi: 10.1080/2162402X.2021.2006893. 
      eCollection 2021.