Background: Somatic mutations in vivo preferentially arise in proliferating (activated) cells. Ex vivo selection of T cells resistant to 6-thioguanine identifies T cells with in vivo hypoxanthine-guanine phosphoribosyltransferase gene mutations (MT). We previously reported that MT from melanoma patients are enriched for proliferating T cells that persist in blood and infiltrate the tumor. We hypothesize that T cells identified in vivo at sites of tumor (i.e. melanoma-associated T cells) will persist in MT following successful treatment with immune checkpoint blockade. Methods: Persistence of melanoma-associated T cells in uncultured (T0) peripheral blood mononuclear cells (PBMC) and in PBMC expanded with (MT) or without (wild-type (WT)) 6-thioguanine selection was examined in a metastatic melanoma patient who achieved a durable antitumor response following 2 intratumoral α-gal glycolipid injections (IT-AG) followed by Ipilimumab (Ipi) every 3 weeks for 4 doses given 4 weeks later at a time of disease progression. TCR beta chain (TRB) repertoire was examined in melanoma-associated T cells from a tumor sample obtained ~20 months prior to IT-AG (T-T0) and also in T0, WT, and MT from PBMC obtained before and 4-weeks after IT-AG as well as 1-, 4-, and 13-months post-Ipi via 5’ RACE and Illumina MiSeq sequencing. Results: The patient achieved a durable antitumor response, and several expanded or activated T cell clones persisted in this patient in T0, WT, and MT. Identical TRB were observed between MT and WT and T0, and expansions and contractions of T cell clones were noted over time. TRB identified in T-T0 persisted in the blood with identical TRBs identified in T0, WT, and MT. Detection rates of TRB shared between T-T0 and MT, WT, or T0 (any timepoints) were 11.0 % (72/656), 1.5 % (206/13,639), and 1.3 % (381/29,807), respectively (p = 10^-7 by Monte Carlo computations for the MT vs WT and MT vs T0 comparisons). Conclusions: MT are enriched for melanoma-associated T cells following successful treatment of a melanoma patient with immune checkpoint blockade and merit further study as a biomarker of response to immunotherapy.