Background: The brain is considered as an immuno-privileged organ and little is known about the inflammatory response to melanoma BM. Methods: Patients with neurosurgical resected and histologically verified melanoma BM were identified. Investigation of PD1, PD-L1, CD3, CD8, CD45RO and BRAF V600E were performed by immunohistochemistry and analyzed using previously published semiquantitative evaluation criteria. Results: Forty-six specimens (28/46; 60.9% BRAF V600E positive) were available. Forty-one/46 (89.1%) specimens presented with TIL infiltration. CD3+ TILs were evident in 35/46 (76.1%), CD8+ TILs in 28/46 (60.9%), CD45RO+ TILs in 32/46 (69.6%) and PD1+ TILs in 28/46 (60.9%) specimens. The Table lists details of TIL infiltration density. PD-L1 expression on melanoma BM tumor cells was observed in 21/46 (45.7%) specimens. Median H-score for PD-L1 was 3 (range 1–90). Eight/21 (38.1%) PD-L1 positive specimens presented with an H score over 5 %. PD-L1 expression on tumor cells was associated with higher density of PD1+ (p=0.002), CD3+ (p=0.024) and CD8+ (p=0.050) TIL infiltration. Furthermore, density of CD3+ TILs was associated with density of CD8+ (p<0.001), PD1+ (p<0.001) and CD45RO+ (p<0.001) TILs, respectively. No association of previous systemic antineoplastic therapy (including chemotherapy and interferon) and expression of PD-L1, PD1, CD3 or CD45RO could be observed (p=n.s). Expression of PD-L1 on tumor cells or density of PD1+, CD3+, CD8+ or CD45RO+ TILs did not correlate with BRAF V600E status (p=n.s.) or survival from first diagnosis of BM (p=n.s.). Conclusions: Melanoma BM show considerable inflammatory infiltrates and expression of PD1 and PD-L1. Clinical studies should investigate the value of checkpoint inhibitors in patients with melanoma brain metastases.