BNCT Triggers Immunogenic Cell Death in B16 Melanoma Without Accompanying T-Cell Infiltration--Implications for Combination Immunotherapy

BNCT in C57BL/6 mice bearing B16 melanoma significantly suppressed tumor growth and prolonged survival, inducing ICD markers and Th1 cytokines without increasing intratumoral CD8+ T cells.

• Why it matters: Immunologically “cold” tumors often exclude effector T cells, so even immune activation from therapy may not translate into local antitumor immunity.
• What they did: In a B16 melanoma mouse model, mice received BPA (500 mg/kg) with neutron irradiation for 10 or 20 min (BNCTN10/BNCTN20), and the best regimen (BNCTN20) was analyzed on days 3 and 7 using histology, DNA damage/apoptosis and immune marker staining, cytokine/chemokine ELISA, and 10B distribution by ICP-OES.
• The result: BNCTN20 achieved TGI ~ 88.9% (p < 0.001) with longer survival (p < 0.001) and increased gamma-H2AX, HMGB1, cleaved caspase-3, PD-L1, and CXCL9/10 signaling, but CD8+ infiltration and granzyme B did not rise, suggesting PD-L1–linked adaptive resistance.

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