Association of pretreatment immune microenvironment profile with boron neutron capture therapy efficacy in cutaneous tumors: results from an ancillary multiplex immunofluorescence study

Abstract

Boron neutron capture therapy (BNCT), an emerging novel radiotherapy modality, has shown immunological relevance in preclinical models. Although the safety and efficacy of BNCT for cutaneous tumors have been evaluated in a Phase I clinical trial, studies using human clinical specimens remain limited. In this exploratory translational study, we aimed to investigate pretreatment immune microenvironmental features in patients treated with BNCT and to descriptively assess their relationship with clinical response. To this end, formalin-fixed paraffin-embedded pretreatment biopsy samples obtained from a Phase I clinical trial of BNCT for cutaneous tumors were analyzed in three responders and three non-responders. Multiplex immunofluorescent staining was performed using CD8+ T-cell and dendritic cell (DC) antibody panels to assess the phenotypes and spatial relationships of immune cells within the tumor microenvironment. At baseline, responders tended to show higher densities of total T cells, CD8+ T cells, DCs and mature DC-like cells than non-responders. CD8+ T cells in responders tended to include higher proportions of granzyme B+ and programmed cell death protein 1-positive cells, and spatial analysis showed closer proximity between CD8+ T cells and mature DC-like cells. In contrast, the proportions of programmed death-ligand 1-positive cells among DCs and tumor cells were higher in non-responders than in responders. These descriptive findings suggest that pretreatment immune microenvironmental features may warrant further investigation as potential factors related to clinical response to BNCT.