1007 Spatial Immunophenotypic Changes in Chordoma Tumor Microenvironment Following PD-1 Blockade: Evidence of Increased T Cell Density but Sustained Tumor Evasion

Le résumé fourni par la source

INTRODUCTION: Chordomas are rare, locally aggressive malignant notochordal remnant tumors resistant to conventional therapies. Immune checkpoint inhibitors, such as nivolumab, a programmed death-1 (PD-1) blocker, have shown some promise; however, the impact of such therapies on the chordoma microenvironment (TME) has not been studied. METHODS: Patient-matched chordoma specimens obtained before (n = 3) and after (n = 4) nivolumab treatment were profiled with spatial multiplex immunofluorescence. To characterize changes in the TME as a function of nivolumab, the following parameters were analyzed: distance between cell phenotypes; density of specific phenotypes; and proportional composition of local cell microenvironments. A significance threshold of a = 0.05 was used after the Bonferroni correction. Clinical annotation was obtained through retrospective review. RESULTS: All patients had disease progression after surgery, radiotherapy, and nivolumab treatment. Single-cell multiplex immunofluorescence revealed that although there was increased immune cell infiltration after nivolumab treatment, immune cells were confined to tumor-absent fibrous septa. Quantitative analyses found that while the distance between immune cells decreased after nivolumab treatment, the distance between immune cells and tumor cells increased. the density coverage of CD4+ and CD8+ T cells around tumor cells did increase post-nivolumab from 2.5 to 14.9 c/mm2 (p < 0.0001) and 1.7 to 10.4 c/mm2 (p < 0.0001), respectively; however, only the proportion of CD8+ T cells increasing minimally from 0.001 to 0.003 (p = 0.0010) as a function of nivolumab treatment within the local immune environment of tumor cells. CONCLUSIONS: Overall, we found that post-nivolumab immune cell lineages clustered together without significant tumor cell interactions, suggesting that PD-1 blockade did not induce a sufficient direct cell-mediated cytotoxic effect nor antigen presentation events.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.