TY - JOUR
T1 - Enrichment of Tumor-Infiltrating B Cells in Group 4 Medulloblastoma in Children
AU - Wu, Kuo Sheng
AU - Jian, Ting Yan
AU - Sung, Shian Ying
AU - Hsieh, Chia Ling
AU - Huang, Man Hsu
AU - Fang, Chia Lang
AU - Wong, Tai Tong
AU - Lin, Yu Ling
N1 - Funding Information:
Funding: This research was funded by the Ministry of Science and Technology (MOST 110-2320-B-001 -012 -MY3 and MOST 108-2314-B-038-061-MY3), Ministry of Health and Welfare (MOHW111-TDU-B-221-114017), the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) (DP2-110-21121-03-C-02-01 and DP2-110-21121-03-C-02-02), and Taipei Medical University Hospital (109TMU-TMUH-15).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Medulloblastoma (MB) is the most common malignant brain tumor in children. It is clas-sified into core molecular subgroups (non-wingless activated (WNT), sonic hedgehog activated (SHH), Group 3 (G3), and Group 4 (G4)). In this study, we analyzed the tumor-infiltrating immune cells and cytokine profiles of 70 MB patients in Taiwan using transcriptome data. In parallel, immune cell composition in tumors from the SickKids cohort dataset was also analyzed to confirm the findings. The clinical cohort data showed the WNT and G4 MB patients had lower recurrence rates and better 5-year relapse-free survival (RFP) compared with the SHH and G3 MB patients, among the four subgroups of MB. We found tumor-infiltrating B cells (TIL-Bs) enriched in the G4 subgroups in the Taiwanese MB patients and the SickKids cohort dataset. In the G4 subgroups, the patients with a high level of TIL-Bs had better 5-year overall survival. Mast cells presented in G4 MB tumors were positively correlated with TIL-Bs. Higher levels of CXCL13, IL-36γ, and CCL27 were found compared to other subgroups or normal brains. These three cytokines, B cells and mast cells contributed to the unique immune microenvironment in G4 MB tumors. Therefore, B-cell enrichment is a G4-subgroup-specific immune signature and the presence of B cells may be an indica-tor of a better prognosis in G4 MB patients.
AB - Medulloblastoma (MB) is the most common malignant brain tumor in children. It is clas-sified into core molecular subgroups (non-wingless activated (WNT), sonic hedgehog activated (SHH), Group 3 (G3), and Group 4 (G4)). In this study, we analyzed the tumor-infiltrating immune cells and cytokine profiles of 70 MB patients in Taiwan using transcriptome data. In parallel, immune cell composition in tumors from the SickKids cohort dataset was also analyzed to confirm the findings. The clinical cohort data showed the WNT and G4 MB patients had lower recurrence rates and better 5-year relapse-free survival (RFP) compared with the SHH and G3 MB patients, among the four subgroups of MB. We found tumor-infiltrating B cells (TIL-Bs) enriched in the G4 subgroups in the Taiwanese MB patients and the SickKids cohort dataset. In the G4 subgroups, the patients with a high level of TIL-Bs had better 5-year overall survival. Mast cells presented in G4 MB tumors were positively correlated with TIL-Bs. Higher levels of CXCL13, IL-36γ, and CCL27 were found compared to other subgroups or normal brains. These three cytokines, B cells and mast cells contributed to the unique immune microenvironment in G4 MB tumors. Therefore, B-cell enrichment is a G4-subgroup-specific immune signature and the presence of B cells may be an indica-tor of a better prognosis in G4 MB patients.
KW - G4 subgroup
KW - mast cells
KW - medulloblastoma
KW - tumor-infiltrating B cells
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U2 - 10.3390/ijms23095287
DO - 10.3390/ijms23095287
M3 - Article
AN - SCOPUS:85129598450
SN - 1661-6596
VL - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 9
M1 - 5287
ER -