A functional level we showed that CD74 regulates tumor cell HLA class II immune peptidome complexity, which might be a central immunological event to get a clinically relevant HLA class II restricted anti-tumor response in BM. To answer this question appropriately, the exact function of CD74 in tumor cells for functional immune responses including the influence on the function of various effector cell subsets like TILs and NKcells has to be addressed in detail in added studies. HLA class II peptidome analyses in patient samples of CD74high versus CD74low expressors are likewise extremely relevant and unfortunately a technical limitation of your present study. Additionally, given that recent research point out the importance of an unimpaired antigen-processing machinery for a successful immunotherapy response [35] CD74 in cancer cells need to also be explored as a putative predictive marker for immunotherapies.Zeiner et al. Acta Neuropathologica Communications (2018) 6:Page 14 ofAdditional filesAdditional file 1: Figure S1. Clinical data on the distinct BM cohorts and association of CD74 expression with clinical parameters. Correlation analyses have been performed making use of Spearmen’s correlation analyses (Spearmen’s and corresponding p-values are depicted). (JPEG 1333 kb) More file two: Figure S2. CD74 expression in distinctive stages of melanoma (a, b) and NSCLC (c). Matched-pairs analysis of primary tumors and BM (distinct key tumor entities) (d). (JPEG 1243 kb) More file 3: Figure S3. (a) HLA class II dependent Kaplan-Meier survival analyses in the total BM cohort as well as inside the two largest subcohorts of NSCLC and melanoma. (b) Matched-pairs analysis of principal tumors and BM (different primary tumor entities). (JPEG 2138 kb) More file 4: Table S1. Table displaying differentially methylated CpGs amongst BM of NSCLC having a very functional immune response, defined as CD74high and TILhigh tumors (CD74 TIL high) and tumors not showing both of those attributes (CD74 TIL low). (CSV 1 kb) Acknowledgments MM would like to thank the Luxembourg National Analysis Fond (FNR) for the assistance (FNR PEARL P16/BM/11192868 grant). Authors’ contributions PSZ performed in vitro too as in vivo experiments making use of cell culture and paraffin-embedded tissue, analyzed information, wrote the GAS6 Protein Human manuscript and was involved in the study design and conception. JZ performed in vitro at the same time as in vivo experiments making use of cell lines and paraffin-embedded tissue, analyzed data, wrote the manuscript and was involved inside the study style and conception. DJK carried out HLA peptidome analyses, wrote the manuscript and was involved within the study design and style. SB performed in vivo analyses on tissue microarrays. JT and MWR offered clinical data and performed image analyses. FT and AB performed cell line characterizations. MTF supplied tissue and clinical data. AM performed bioinformatic analyses. JPS provided and analyzed clinical information. RB analyzed tissue specimens and provided clinical data. JW wrote the manuscript and was involved in study style and conception. HMK analyzed tissue specimens and provided clinical information. KHP analyzed tissue specimens, provided equipment and wrote the manuscript. SS offered equipment and analyzed HLA peptidome information. BW supplied clinical information, performed human information analyses and was involved in study design and conception. MM analyzed human information, wrote the manuscript and was involved in study design and conception. PNH supervised and conceived the study, performed.