Immu-01. immune phenotyping of brain metastasis patients identifies a distinct depletion and exhaustion phenotype of the cd4 t cells in blood and bone marrow

Abstract Brain metastases are the most rapidly emerging entity in neuro-oncology. Given the decisive role of immunotherapy, the immune crosstalk between the blood circulation and the brain tumor requires deeper investigation, especially in light of recent data showing that T cells might be trapped in the bone marrow during the metastasis process. We analyzed the immune profile in the peripheral blood and in the bone marrow in a cohort of 40 patients with brain metastasis using flow cytometry. Our results show a global decrease in the proportion of CD3+ T cells in the peripheral blood of patients with brain metastases when compared to healthy donors (HD). CD4+ T cells were more affected by the presence of brain metastases than CD8 cells, with a significant decrease in Tregs, Th1 and Th2 helper cell populations. The proportion of naïve CD4 T cells with low expression of CXCR3 and CD127 is decreased in tumor, while a subpopulation of naïve as well as central memory CD4CM with high expression of PD1 is increased in brain metastasis patients compared to HD. Additionally, we noticed an increase in the proportion of B cells in the patient’ blood, together with a decrease in non-classical CD86+ monocytes compared to HD. The NK cell population was also affected with a significant depletion of mature NK CD57+ in the blood of patients with brain metastases. In the bone marrow, we found an increase in the proportion of senescent CD4CM CD57+ in patients with NSCLC brain metastasis, while the proportion of CD4CM CXCR3+ was significantly decreased compared to HD. Taken together, our data show that brain metastases profoundly affect the phenotype and abundance CD4+ T cells in the periphery and bone marrow, thus interfering with the primary T cell population orchestrating the tumor-specific immune response.