PMID- 28254787
OWN - NLM
STAT- MEDLINE
DCOM- 20180608
LR  - 20181113
IS  - 2326-6074 (Electronic)
IS  - 2326-6066 (Print)
IS  - 2326-6066 (Linking)
VI  - 5
IP  - 4
DP  - 2017 Apr
TI  - Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells.
PG  - 319-329
LID - 10.1158/2326-6066.CIR-16-0141 [doi]
AB  - Immunotherapies targeting immune checkpoints have proven efficacious in reducing 
      the burden of lung cancer in patients; however, the antigenic targets of these 
      reinvigorated T cells remain poorly defined. Lung cancer tumors contain 
      tumor-associated macrophages (TAM) and neutrophils, which release the serine 
      proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor 
      microenvironment. NE and P3 shape the antitumor adaptive immune response in 
      breast cancer and melanoma. In this report, we demonstrate that lung cancer cells 
      cross-presented the tumor-associated antigen PR1, derived from NE and P3. 
      Additionally, NE and P3 enhanced the expression of human leukocyte antigen (HLA) 
      class I molecules on lung cancer cells and induced unique, endogenous peptides in 
      the immunopeptidome, as detected with mass spectrometry sequencing. Lung cancer 
      patient tissues with high intratumoral TAMs were enriched for MHC class I genes 
      and T-cell markers, and patients with high TAM and cytotoxic T lymphocyte (CTL) 
      infiltration had improved overall survival. We confirmed the immunogenicity of 
      unique, endogenous peptides with cytotoxicity assays against lung cancer cell 
      lines, using CTLs from healthy donors that had been expanded against select 
      peptides. Finally, CTLs specific for serine proteases-induced endogenous peptides 
      were detected in lung cancer patients using peptide/HLA-A2 tetramers and were 
      elevated in tumor-infiltrating lymphocytes. Thus, serine proteases in the tumor 
      microenvironment of lung cancers promote the presentation of HLA class I 
      immunogenic peptides that are expressed by lung cancer cells, thereby increasing 
      the antigen repertoire that can be targeted in lung cancer. Cancer Immunol Res; 
      5(4); 319-29. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Peters, Haley L
AU  - Peters HL
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Tripathi, Satyendra C
AU  - Tripathi SC
AD  - Department of Clinical Cancer Prevention-Research, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Kerros, Celine
AU  - Kerros C
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Katayama, Hiroyuki
AU  - Katayama H
AD  - Department of Clinical Cancer Prevention-Research, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Garber, Haven R
AU  - Garber HR
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - St John, Lisa S
AU  - St John LS
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Federico, Lorenzo
AU  - Federico L
AD  - Department of Melanoma Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Meraz, Ismail M
AU  - Meraz IM
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Roth, Jack A
AU  - Roth JA
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Sepesi, Boris
AU  - Sepesi B
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Majidi, Mourad
AU  - Majidi M
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Ruisaard, Kathryn
AU  - Ruisaard K
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Clise-Dwyer, Karen
AU  - Clise-Dwyer K
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Roszik, Jason
AU  - Roszik J
AD  - Department of Melanoma Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
AD  - Department of Genomic Medicine, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas.
FAU - Gibbons, Don L
AU  - Gibbons DL
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
AD  - Department of Molecular and Cellular Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Heymach, John V
AU  - Heymach JV
AD  - Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Swisher, Stephen G
AU  - Swisher SG
AD  - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Bernatchez, Chantale
AU  - Bernatchez C
AD  - Department of Melanoma Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Alatrash, Gheath
AU  - Alatrash G
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas.
FAU - Hanash, Samir
AU  - Hanash S
AD  - Department of Clinical Cancer Prevention-Research, The University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Molldrem, Jeffrey J
AU  - Molldrem JJ
AD  - Department of Stem Cell Transplantation and Cellular Therapy, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas. jmolldre@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - T32 CA009598/CA/NCI NIH HHS/United States
GR  - P50 CA100632/CA/NCI NIH HHS/United States
GR  - P50 CA070907/CA/NCI NIH HHS/United States
GR  - P01 CA049639/CA/NCI NIH HHS/United States
GR  - P01 CA148600/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170302
PL  - United States
TA  - Cancer Immunol Res
JT  - Cancer immunology research
JID - 101614637
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - EC 3.4.- (Serine Proteases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen Presentation/*immunology
MH  - Antigens, Neoplasm/*immunology
MH  - Biomarkers
MH  - Cell Line, Tumor
MH  - Cytokines/metabolism
MH  - HLA-A2 Antigen/genetics/immunology/metabolism
MH  - Histocompatibility Antigens Class I/genetics/immunology/metabolism
MH  - Humans
MH  - *Immunomodulation
MH  - Immunophenotyping
MH  - Leukocytes, Mononuclear/immunology/metabolism
MH  - Lung Neoplasms/*immunology/*metabolism/pathology
MH  - Lymphocyte Activation
MH  - Peptides/chemistry/immunology/metabolism
MH  - Serine Proteases/*metabolism
MH  - T-Lymphocyte Subsets/immunology/metabolism
PMC - PMC5673248
MID - NIHMS857562
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2017/03/04 06:00
MHDA- 2018/06/09 06:00
PMCR- 2018/04/01
CRDT- 2017/03/04 06:00
PHST- 2016/06/27 00:00 [received]
PHST- 2016/07/28 00:00 [revised]
PHST- 2017/02/27 00:00 [accepted]
PHST- 2017/03/04 06:00 [pubmed]
PHST- 2018/06/09 06:00 [medline]
PHST- 2017/03/04 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - 2326-6066.CIR-16-0141 [pii]
AID - 10.1158/2326-6066.CIR-16-0141 [doi]
PST - ppublish
SO  - Cancer Immunol Res. 2017 Apr;5(4):319-329. doi: 10.1158/2326-6066.CIR-16-0141. 
      Epub 2017 Mar 2.