PMID- 32761425
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 69
IP  - 12
DP  - 2020 Dec
TI  - Increased Th17 activation and gut microbiota diversity are associated with 
      pembrolizumab-triggered tuberculosis.
PG  - 2665-2671
LID - 10.1007/s00262-020-02687-5 [doi]
AB  - INTRODUCTION: A hypersensitivity response akin to immune reconstitution 
      inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for 
      anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced 
      activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought 
      to be linked to pulmonary inflammation through the gut-lung axis. MATERIALS AND 
      METHODS: We used ImmuCellAI to investigate the T cell population in lung cancer 
      and tuberculosis samples. Then, we applied flow cytometry to monitor the 
      expression levels of the Th17 cell activation marker CD38 in the peripheral blood 
      of a patient experiencing adverse events, including tuberculosis, in response to 
      pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine 
      the alterations caused by pembrolizumab. RESULTS: The percentage of Th17 cells 
      was increased in both lung cancer and tuberculosis. FACS analysis showed that 
      pembrolizumab induced substantial CD38 expression in Th17 cells. The patient's 
      fecal samples showed that the diversity of the gut microbiota was significantly 
      increased in response to the pembrolizumab cycle. One enriched genus was 
      Prevotella, which has previously been linked to lung inflammation and Th17 immune 
      activation. DISCUSSION: The observed Th17 activation in our patient was 
      consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered 
      tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 
      phenotype through microbiota interactions in the gut-lung axis.
FAU - Zhang, Yun-Bin
AU  - Zhang YB
AD  - Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular 
      Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
FAU - Liu, Shi-Jia
AU  - Liu SJ
AD  - Department of Pulmonary Disease, PLA 905 Hospital, 9585 Humin Road, Shanghai, 
      200235, China.
FAU - Hu, Zhi-Dong
AU  - Hu ZD
AD  - Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular 
      Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
FAU - Zhou, Ji-Xue
AU  - Zhou JX
AD  - Department of Pulmonary Disease, PLA 905 Hospital, 9585 Humin Road, Shanghai, 
      200235, China.
FAU - Wang, Yin-Zhen
AU  - Wang YZ
AD  - Department of Pulmonary Disease, PLA 905 Hospital, 9585 Humin Road, Shanghai, 
      200235, China.
FAU - Fang, Bing
AU  - Fang B
AD  - Department of Pulmonary Disease, PLA 905 Hospital, 9585 Humin Road, Shanghai, 
      200235, China.
FAU - Wong, Ka-Wing
AU  - Wong KW
AD  - Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular 
      Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China. 
      kwwong@gmail.com.
FAU - Xia, Fan
AU  - Xia F
AUID- ORCID: 0000-0003-3932-6465
AD  - Department of Pulmonary Disease, PLA 905 Hospital, 9585 Humin Road, Shanghai, 
      200235, China. xfs2000@hotmail.com.
LA  - eng
GR  - 81371777/Natural Science Foundation of China/
GR  - 81873884/Natural Science Foundation of China/
GR  - 81770010/Natural Science Foundation of China/
PT  - Case Reports
PT  - Journal Article
DEP - 20200806
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antitubercular Agents)
RN  - 0 (DNA, Bacterial)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (RNA, Ribosomal, 16S)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Antitubercular Agents/therapeutic use
MH  - DNA, Bacterial/isolation & purification
MH  - Datasets as Topic
MH  - Gastrointestinal Microbiome/genetics/*immunology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/blood/chemically 
      induced/*immunology/microbiology
MH  - Lung/diagnostic imaging/immunology/microbiology/pathology
MH  - Lung Neoplasms/blood/*drug therapy/immunology/microbiology
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium tuberculosis/immunology/isolation & purification
MH  - Prevotella/genetics/immunology/isolation & purification
MH  - Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
MH  - RNA, Ribosomal, 16S/genetics
MH  - Th17 Cells/drug effects/*immunology
MH  - Tomography, X-Ray Computed
MH  - Tuberculosis/chemically induced/drug therapy/*immunology/microbiology
PMC - PMC11027455
OTO - NOTNLM
OT  - Gut microbiota diversity
OT  - Immune reconstitution inflammatory syndrome (IRIS)
OT  - Pembrolizumab
OT  - Th17 activation
OT  - Tuberculosis
COIS- All authors declare no conflict of interest.
EDAT- 2020/08/08 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/08/06
CRDT- 2020/08/08 06:00
PHST- 2020/02/26 00:00 [received]
PHST- 2020/07/30 00:00 [accepted]
PHST- 2020/08/08 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/08 06:00 [entrez]
PHST- 2020/08/06 00:00 [pmc-release]
AID - 10.1007/s00262-020-02687-5 [pii]
AID - 2687 [pii]
AID - 10.1007/s00262-020-02687-5 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2020 Dec;69(12):2665-2671. doi: 
      10.1007/s00262-020-02687-5. Epub 2020 Aug 6.