LINC-30. A CLINICOPATHOLOGICAL STUDY OF IMMUNOGENICITY AND IMMUNE EVASION MECHANISMS AMONG MOLECULAR SUBGROUPS OF MEDULLOBLASTOMA

Abstract

INTRODUCTIONMedulloblastomas have been well characterised in terms of genomics, epigenomics, transcriptomics and recently proteomics. However, there is limited knowledge regarding immunogenicity, immune-microenvironment and immune evasion mechanisms in different molecular subgroups of medulloblastoma. It is important to analyze these parameters to understand tumor progression, prognostic stratification as well as treatment response to available immunotherapeutic drugs.MATERIALS AND METHODSMolecular subgrouping performed by immunohistochemistry(IHC), Nanostring and 850k-methylation array. Immune profile by IHC for CD3, 20, CD8 [tumor infiltrating lymphocytes (TILs)], CD163 [tumor-associated macrophages (TAMs)], and PD-L1 and CTLA-4 [immune checkpoint proteins].RESULTSA total of 35 cases were analyzed with age-range from 1 to 54 years (77% pediatric and 23% adult). 82% cases were located in midline, while rest in cerebellar hemispheres. On molecular subgrouping, MBs were subdivided into 8 WNT, 10 SHH, 8 Group 3 and 9 Group 4. Twenty four cases had follow up, 12 with no evidence of disease while 12 with progressive disease or death. PD-L1 expression ranged from 0% to 20% and included 5SHH, 2WNT and 1Group 3. CTLA4 positive lymphocytes ranged from 0 to 33 in 4 cases: 1WNT, 3 SHH, 1Group4. TILs ranged from 0–220/mm2 with a median of 3. TAMs ranged from 0–60/mm2 with a median of 18. Both TILs and TAMs were significantly higher in SHH subgroup.CONCLUSIONPD-L1 positivity and number of TILs and TAMs were significantly more in SHH-subgroup tumors followed by WNT tumors. CTLA-4 expression did not correlate with subgroups. All parameters showed a positive trend with increasing age.