![]() Significance Statement The bilateral subcutaneous tumor model, where tumor cells were inoculated bilaterally into the backs of mice, is a promising model for temporal analysis of the antitumor response in cancer immunotherapy. These findings suggest that our bilateral tumor model is suitable for temporal monitoring of the TCR repertoire to evaluate temporal and treatment-induced changes in tumor-reactive T cell clones. The similarity of the TCR repertoire in the bilateral dLNs was markedly lower than that in the tumor, suggesting that tumor-reactive T cell clones induced independently in each dLN integrated during recirculation and then infiltrated the tumor. ![]() In addition, the similarity between the bilateral tumors was equivalent to heterogeneity on one side of the tumor. The tumor-infiltrating T cell clones were highly conserved between the bilateral tumors, and the extent of clonal expansion was equivalent. Bilateral tumors with equivalent size and draining lymph nodes (dLNs) were collected 13 days after tumor inoculation to analyze the TCR repertoire of CD4 and CD8 T cells. This study examined the prerequisite for this strategy: the TCR repertoire is conserved between bilateral tumors with the same growth rate. A bilateral tumor model, where tumor cells were inoculated bilaterally into the backs of mice, could be used for temporal analysis of the TCR repertoire. However, the lack of experimental models that allow temporal analysis of the TCR repertoire in the same individual in a homogeneous population limits the understanding of the causal relationship between changes in TCR repertoire and antitumor responses. Temporal analysis of the T cell receptor (TCR) repertoire has been used to monitor treatment-induced changes in antigen-specific T cells in patients with cancer.
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