There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma – both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.
Data presented underscores the need for systematic referrals using electronic health records for patients with CHD in order to increase overall CR referral and participation rates of minority populations and other vulnerable groups. Educational programs that target healthcare provider biases towards racial and ethnic groups may help attenuate observed disparities. Alternative modalities such as home-based and internet-based CR programs may also help improve CR participation rates among vulnerable populations.
The path to a surgical career as experienced by African American and Latino surgeons is heavily influenced by mentors mediating their integration into surgical culture and engendering a feeling of belonging. Future surgeons from groups underrepresented in medicine would benefit from identifying aspirational figures early, a structured introduction into the rigors of the profession, and a deconstruction of negative surgical norms.
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