Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression.
Neoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here, we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors.
Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michel
M
DuPage
Ann F
AF
Cheung
Claire
C
Mazumdar
Monte M
MM
Winslow
Roderick
R
Bronson
Leah M
LM
Schmidt
Denise
D
Crowley
Jianzhu
J
Chen
Tyler
T
Jacks
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology; D002452:Cell Count; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D013997:Time Factors; D014185:Transplantation, Isogeneic / Q000276:immunology / Q000473:pathology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; D019496:Cancer Vaccines; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D053699:Interleukin-7 Receptor alpha Subunit; C111390:OVA 323-339; C110366:OVA-8; D009842:Oligopeptides; C491383:Pdcd1 protein, mouse; D010446:Peptide Fragments; D061026:Programmed Cell Death 1 Receptor; C406862:superagonist SIYR; D010047:Ovalbumin
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