Extended Data Figure 1. Patients and mice treated with RT + anti-CTLA4 for melanoma.

a) Twenty-two stage IV melanoma patients (M stage indicated) were stratified by treatment site of a single index metastasis, which was the irradiated tumor. Two dosing levels (DL) for stereotactic body radiation (SBRT) were in each stratum. b) Waterfall plot of the RECIST % change from baseline of unirradiated tumors annotated to indicate metabolic responses by PET/CT (hatches above plot) and response of the irradiated index tumor as measured by CT and PET/CT (hatches below plot). RECIST criteria do not include irradiated tumors. Legend shows color-codes for response after CT or PET/CT (parenthesis). PMD: progressive metabolic disease; SMD: stable metabolic disease; PMR: partial metabolic response; CMR: complete metabolic response. White hatches indicate no imaging obtained. See Extended Data Table 2. c) Survival (right) and total tumor growth (bottom) after RT with either concurrent or sequential anti-CTLA4 compared to anti-CTLA4 (C4) or RT alone. The regimens and the standard regimen used for all other melanoma experiments are illustrated (left). The p-values for tumor growth are compared to anti-CTLA4. d) Survival after RT and/or anti-CTLA4 with or without T cell depletion (n=5–10) using anti-CD8 (CD8). Shown are overall p-values. The p-value for RT + anti-CTLA4 with and without anti-CD8 is p=0.005. Control is an isotype-matched antibody. e) Three mice with CRs were rechallenged with B16-F10 tumors. Shown is a representative mouse. Arrow indicates location of regressed tumor and vitiligo-like condition represented by non-pigmented fur (observed in approximately 50% of mice with CRs). Time line starts from original tumor implantation (day 0) and values above marks are days after first rechallenge. Recurrence occurred only after anti-CD8 treatment and second rechallenge.