CD8 T cell help for innate antitumor immunity.
Innate immunity is considered to initiate adaptive antitumor responses. We demonstrate that monoclonal CD8 T lymphocytes reactive to tumor Ag P1A on P815 mastocytoma cells provide essential "help" to NK cells for rejection of P1A-deficient tumors. RAG-deficient mice have normal NK cells but do not reject either tumor. Reconstitution of these mice with P1A-specific T cells conferred resistance to both P1A-expressing and -deficient tumor cells provided they were present at the same site. Elimination of Ag-negative tumor variants required both activated T and NK cells. Gene expression profiling of NK cells infiltrating P1A-positive tumors in mice with specific CD8 T cells demonstrated an activated effector phenotype. However, CD8 T cell help to NK cells appeared ineffective for P1A-negative variants separated from the P1A-positive tumor. Local tumor Ag-specific T cell-NK cell collaboration results in the elimination of tumor cells whether they express or not the T cell tumor Ag epitope, thus containing the emergence of tumor escape variants before metastasis.
Shanker
Anil
A
Centre d'Immunologie de Marseille-Luminy, Faculté des Sciences de Luminy, Aix-Marseille Université, Marseille, France.
Verdeil
Grégory
G
Buferne
Michel
M
Inderberg-Suso
Else-Marit
EM
Puthier
Denis
D
Joly
Florence
F
Nguyen
Catherine
C
Leserman
Lee
L
Auphan-Anezin
Nathalie
N
Schmitt-Verhulst
Anne-Marie
AM
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D019139:Tumor Escape / Q000276:immunology
D000951:Antigens, Neoplasm; D018398:Homeodomain Proteins; C507749:cancer-testis antigen P1A, mouse; C076546:tumor rejection antigen P815A, mouse; C064658:RAG-1 protein