PMID- 30253331
OWN - NLM
STAT- MEDLINE
DCOM- 20190215
LR  - 20190215
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 64
DP  - 2018 Nov
TI  - MYD88 L265P mutation promoted malignant B cell resistance against T cell-mediated 
      cytotoxicity via upregulating the IL-10/STAT3 cascade.
PG  - 394-400
LID - S1567-5769(18)30674-X [pii]
LID - 10.1016/j.intimp.2018.09.024 [doi]
AB  - The myeloid differentiation factor 88 (MYD88) signaling plays critical roles in 
      the developments of B cells. Recent studies demonstrated that in the activated B 
      cell subtype of diffuse large B cell lymphoma (DLBCL), approximately one-third of 
      the patients harbored somatically acquired MyD88 L265P mutation in their 
      lymphomas. It remains unclear whether B cell lymphomas with MYD88 L265P mutation 
      respond differently toward CD8(+) T cell-mediated cytotoxicity. Here, we 
      demonstrated that, when incubated with autologous CD8(+) T cells, the MYD88 L265P 
      mutant lymphomas were more resistant to granzyme B- and perforin-mediated killing 
      than MYD88 wild-type (WT) lymphomas. Interestingly, in the absence of autologous 
      lymphomas, the granzyme B and perforin expression levels in CD8(+) T cells from 
      patients with MYD88 WT lymphomas and from patients with MYD88 L265P mutant 
      lymphomas were comparable; however, in the presence of autologous lymphomas, the 
      CD8(+) T cells from patients with MYD88 L265P mutant lymphomas presented 
      significantly lower granzyme B and perforin expression than CD8(+) T cells from 
      patients with MYD88 WT lymphomas. We further found that the IL-10 expression 
      level and the STAT3 activation level were significantly higher in MYD88 L265P 
      mutant lymphomas than in MYD88 WT lymphomas. Suppressing IL-10 significantly 
      reduced STAT3 activation in both MYD88 WT and MYD88 L265P mutant lymphomas. 
      Blocking either STAT3 or IL-10 could significantly increase the susceptibility of 
      MYD88 L265P mutant lymphomas toward CD8(+) T cell-mediated cytotoxicity. 
      Together, these data revealed a mechanism of immune evasion in MYD88 L265P mutant 
      lymphomas.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Qiu, Huiying
AU  - Qiu H
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Gong, Shenglan
AU  - Gong S
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Xu, Lili
AU  - Xu L
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Cheng, Hui
AU  - Cheng H
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Gao, Lei
AU  - Gao L
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Chen, Jie
AU  - Chen J
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Hu, Xiaoxia
AU  - Hu X
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China.
FAU - Yang, Jianmin
AU  - Yang J
AD  - Department of Haematology, Institute of Haematology, Changhai Hospital, Second 
      Military Medical University, Shanghai, China. Electronic address: 
      chyangjianmin@163.com.
LA  - eng
PT  - Journal Article
DEP - 20180922
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (IL10 protein, human)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Aged
MH  - B-Lymphocytes
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - *Cytotoxicity, Immunologic
MH  - Female
MH  - Humans
MH  - Interleukin-10/*physiology
MH  - Lymphoma, Large B-Cell, Diffuse/genetics/*immunology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Myeloid Differentiation Factor 88/*genetics
MH  - STAT3 Transcription Factor/*physiology
MH  - Tumor Escape
OTO - NOTNLM
OT  - DLBCL
OT  - IL-10
OT  - MYD88
OT  - STAT3
EDAT- 2018/09/27 06:00
MHDA- 2019/02/16 06:00
CRDT- 2018/09/26 06:00
PHST- 2018/07/10 00:00 [received]
PHST- 2018/09/04 00:00 [revised]
PHST- 2018/09/17 00:00 [accepted]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2019/02/16 06:00 [medline]
PHST- 2018/09/26 06:00 [entrez]
AID - S1567-5769(18)30674-X [pii]
AID - 10.1016/j.intimp.2018.09.024 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2018 Nov;64:394-400. doi: 10.1016/j.intimp.2018.09.024. Epub 
      2018 Sep 22.