CART-30

In this study, we evaluated the efficacy and safety of a triplet regimen consisting of the histone deacetylase inhibitor chidamide, decitabine and anti-PD-1 camrelizumab (CDP) in 52 patients with relapsed/refractory cHL who had previously received DP therapy (NCT04233294)...The classical CD30+ HRS-like cells interacted with the abundant immunosuppressive IL21+CD4+ T helper cells, forming a positive feedback loop that supported their survival...CDP treatment promoted the activation of diverse tumor-reactive CD8+ T cells and suppressed the proliferation of IL21+CD4+ T cells by inhibiting STAT1/3 signaling, thereby alleviating their immunosuppressive effects. These findings provide insights into the cHL microenvironment that contributes to anti-PD-1 resistance and highlight the therapeutic effectiveness of dual epi-immunotherapy in overcoming immunotherapy resistance.

For programmed death-ligand 1 (PD-L1), CD8 (cytotoxic T-cell marker), CD68 (macrophage pan-marker), CD64 (FcγRΙ), and CD30, mIHC samples were stained using Opal 7-Color IHC kit. Conclusions : Tislelizumab demonstrated a high CR rate regardless of the FcγRΙ expressing macrophage abundance in the cHL tumor microenvironment, which may be a functional consequence of its engineered Fc region and may differentiate its MOA from the MOAs of other anti-PD-1 agents. CD8+ T-cell abundance and tumor inflammatory gene signatures in the microenvironment may be associated with higher CR rate for cHL patients treated with tislelizumab.