Transcription profiling of mouse CD8 T cells in response to P1A antigen expressing tumor cells or cells not expressing 1A antigen

ABSTRACT: Activation status of CD8 T cells in response to a tumor challenge. Although both natural killer (NK) cells and CD8 T cells are capable of anti-tumor responses, Recombinase Activating Gene (RAG)-deficient mice, which have a normal component of NK cells, are incapable of rejecting the P815 mastocytoma tumor. We established a model where monoclonal CD8 T cell reactivity was restricted to the tumor antigen (Ag) P1A expressed on the P815 mastocytoma. Reconstitution of the RAG-deficient mice with these (TCRP1A) T cells conferred resistance to tumor growth selectively for the P1A-expressing, but not for a P1A-negative variant of P815. Nevertheless, TCRP1A CD8 T cells were efficient and necessary to promote the NK cell dependent rejection of P1A-negative tumors when both P1A-positive and -negative tumors were present at the same site. Gene expression profiling in NK cells infiltrating the P1A-positive, as compared to the P1A-negative tumor, in mice transferred with TCRP1A CD8 T cells established their acquisition of an activated effector phenotype. Help from CD8 T cells was provided locally, as it did not induce activation of NK cells present in a P1A-negative variant at a distant site, nor the rejection of this variant. These results illustrate a mechanism by which, in the face of immunoselection / editing, the synergy between specific anti-tumor Ag T cells and NK cells can contribute to the elimination of tumor cells whether or not they express the tumor Ag. This mechanism appears ineffective, however, once tumor variants lacking the tumor Ag are separated from the wild-type tumor, as would be the case in tumor metastasis.

INSTRUMENT(S): BAS-5000 [FUJIFILM]

ORGANISM(S): Mus musculus

SUBMITTER: Gregory Verdeil 

PROVIDER: E-MEXP-1285 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress