B7-H1/PD-1 signals in carcinoma and lymphoma immunopathogenesis and immunotherapy (VAC12P.1118)

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Abstract αB7-H1 (αPD-L1) reportedly treats cancer by blocking PD-1 signals, but few formal data are reported. We showed B16 melanoma is CD80-PD-1-B7-H1+. αB7-H1 slowed subcutaneous (SQ) B16 in wild type (WT), B7-H1 KO and CD80 KO, with little difference between groups. αB7-H1 did not slow B16/B7-H1lo tumors in B7-H1 KO mice, formally showing tumor B7-H1 mediates αB7-H1 effects. αPD-1 slowed B16 in WT or B7-H1 KO, but not B16/B7-H1lo in B7-H1 KO, formally showing B7-H1/PD-1 effects in αB7-H1. Tumor B7-H1 variably predicts αB7-H1 efficacy, possibly due to variable tumor B7-H1 expression. To model variable B7-H1, we gave B16 or B16/B7-H1lo on both flanks, or each on opposite flanks of the same WT mice. αB7-H1 slowed B16, but not B16/B7-H1lo, unless B16 was on the other flank, suggesting spread of anti-tumor immunity, helping explain variable αB7-H1 effects by tumor B7-H1 status. We found EL4 T cell lymphoma is CD80loB7-H1loPD-1hi. αB7-H1 and αPD-1 did not slow SQ EL4. Unexpectedly, EL4/B7-H1hi exhibited significant growth delay after SQ or intravenous challenge in WT. EL4/B7-H1hi grew well in vitro, but in clusters as opposed to EL4. αPD-1 or αB7-H1 in vitro blocked clusters but such pre-treated cells still grew slowly in vivo suggesting negative inter-cell B7-H1/PD-1 signals. Our data formally show B7-H1/PD-1 signals in αB7-H1 treatment effects, help explain variable αB7-H1 effects by tumor B7-H1 status, and suggest novel and specific effects in T cell lymphomas requiring more study.