Immune microenvironment of intimal sarcomas: Adaptive immune resistance with potential therapeutic implications.

Intimal sarcomas are rare, aggressive neoplasms that arise from large blood vessels. Characterization of the tumor immune microenvironment may suggest new treatment strategies. Seventeen specimens from 7 patients were labeled by immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), CD45, CD8, CD4, FOXP3, CD20, CD68, and LAG3. The immune cell density was scored as a percentage of the tumor area (1+ [<5%], 2+ [5%-50%], 3+ [>50%]); PD-L1 expression was scored on tumor cells and on intratumoral immune cells. Immune marker density was quantified using image analysis software. All intimal sarcomas showed immune cell infiltration (41% were 1+, 53% were 2+, 6% were 3+). Tumor and immune cell PD-L1 labeling was seen in 35% and 76% of cases, respectively; PD-L1+ intimal sarcomas had higher CD45+, CD8+, FOXP3+, CD68+, and leukocyte activation gene 3 (LAG3)+ cell densities (P ≤ .01). Similarly, PD-L1 expression on immune cells correlated with higher densities of CD8+ and FOXP3+ cells (P < .04). Higher LAG3+ cell density correlated with higher CD68+ cell density and necrosis (P < .05). One patient with prolonged survival had the highest immune cell density and PD-L1 expression. These data show that intimal sarcomas have an active tumor microenvironment with an adaptive pattern of PD-L1 expression. Our results suggest that immunotherapy may be an effective treatment option.

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