Anti-tumor memory CD4 and CD8 T-cells quantified by bulk T-cell receptor (TCR) clonal analysis

Simple, reliable methods to detect anti-tumor memory T-cells are necessary to develop a clinical tumor vaccination program. A mouse model of curative viral onco-immunotherapy found that peritoneal tumor challenge following cure identified an oligoclonal anti-tumor memory CD4 and CD8 T-cell response. Clonotypes differed among the challenged animals but were congruent in blood, spleen and peritoneal cells (PC) of the same animal. Adoptive transfer demonstrated that the high-frequency responding T-cells were tumor specific. Tetramer analysis confirmed that clonotype frequency determined by T-cell receptor (TCR)- chain (TRB) analysis closely approximated cell clone frequency. The mean frequency of resting anti-tumor memory CD4 T-cells in unchallenged spleen was 0.028% and of memory CD8 T-cells was 0.11% which was not high enough to distinguish them from background. Stimulation produced a mean similar to 10-fold increase in splenic and 100-fold increase in peritoneal anti-tumor memory T-cell clonotypes. This methodology can be developed to use blood and tissue sampling to rapidly quantify the effectiveness of a tumor vaccine or any vaccine generating therapeutic T-cells.

Automated summary

Simple and reliable methods are needed to detect anti-tumor memory T-cells for clinical tumor vaccination. A mouse model of curative viral onco-immunotherapy showed that peritoneal tumor challenge can identify an oligoclonal anti-tumor memory CD4 and CD8 T-cell response. Different clonotypes were found among challenged animals, but were consistent in blood, spleen, and peritoneal cells of the same animal. These findings suggest that this methodology can be used to assess the effectiveness of tumor vaccines or therapeutic T-cell vaccines using blood and tissue sampling.