PD-1 immune checkpoint blockade (ICB) with platinum chemotherapy (ChemoIO) has transformed treatment for resectable non-small cell lung cancer (NSCLC). PD-1 ICB was established to reinvigorate tumor T cells and reduce T cell exhaustion. However, the impact of PD-1 blockade on the induction and maintenance of tumor-relevant tdLN T cells and functional T cell memory in the context of surgical resection is not fully understood. We hypothesize that T cells activated in the tumor-draining lymph node (tdLN) also respond to PD-I ICB. Clonal dynamics were assessed across tissues using single-cell TCR barcoding integrated with transcriptional profiling (scRNA sequencing) by using machine learning (ML) and bioinformatic approaches. Using this approach, we determined the contribution of tumor-specific tdLN T cell clones. In chapter 2, we demonstrate that tdLN-paired clones are less exhausted than clones that are only found in the tumor. We establish that there are two distinct populations of LN-paired clones: those that directly link from the tdLN and tumor (tdLN-tumor paired) with tumor killing capacity, and clones that circulate within the blood with cytotoxic memory surveillance potential. Furthermore, the distinction of these two LN-paired subsets is found in the earliest memory state of expanded tumor-specific tdLN T cells and is reflected in the tumor as similarly more differentiated, effector subsets. ChemoIO was also found to directly impact tdLN-paired clonal diversity and phenotypic differentiation. In chapter 3, we demonstrate that we can further enhance and alter tumor-specific tdLN T cells with the addition of IL15-Ra in a non-small cell lung cancer mouse model. This combination therapy of IL15-Ra and PD-1 ICB increased a cytotoxic KILR effector function within memory-like tdLN T cells and in the effector tumor T cells. Combination therapy of IL15-Ra and PD-1 ICB also increased the proportion of persisting LN-paired clones 30 days after resection. Initial clonal averages KILR function within the tdLN and tumor at the time of resection were increased in clones that persisted versus those that did not. Together, our results indicate that the tdLN not only contributes to anti-tumor response but also has its own response to ICB therapy in addition to the tumor.