PMID- 34448522
OWN - NLM
STAT- MEDLINE
DCOM- 20220915
LR  - 20220929
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 130
IP  - 4
DP  - 2022 Oct
TI  - Predictive value of immunological markers after bacille Calmette-Guerin induction 
      in bladder cancer.
PG  - 444-453
LID - 10.1111/bju.15582 [doi]
AB  - OBJECTIVES: To investigate the predictive value of different immunological 
      markers on treatment outcomes after bacille Calmette-Guerin (BCG) induction in 
      high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: 
      Patients who underwent transurethral resection of bladder tumour for NMIBC were 
      assessed for study eligibility. Urine and blood samples were taken from patients 
      at baseline (immediately before first dose of induction) and after induction (4 h 
      after last [sixth] dose). Urine samples were evaluated for interleukin (IL)-2 and 
      IL-10 by solid-phase enzyme-linked immunosorbent assay. Blood samples were 
      evaluated for tumour necrosis factor alpha (TNF-alpha), cytotoxic T-lymphocyte antigen 4 
      (CTLA-4) and transcription factors (TFs) (GATA-binding protein 3 [GATA3], T-box 
      expressed in T cells [T-bet], and forkhead box protein 3 [FoxP3]) using 
      quantitative reverse transcriptase-polymerase chain reaction analysis. Change 
      pattern and fold change of each evaluable marker was assessed in relation to 
      different treatment outcomes (initial complete response 
      [ICR]/recurrence/progression). RESULTS: Between July 2013 and May 2019, 204 
      patients were included. Among evaluable markers, urinary IL-2 and serum TNF-alpha 
      increased in all patients, serum CTLA-4 and FoxP3(+) showed a predominant 
      decreased pattern in 188 (92.2%) and 192 (94.1%) patients, respectively. An ICR 
      was achieved in 186 (91.2%) patients. Serum TNF-alpha fold change and urinary IL-10 
      change pattern were significantly associated with an ICR (P = 0.001 and P = 0.03, 
      respectively). At a median (range) follow-up of 37 (20-88) months, 104 (56%) 
      patients developed recurrence. Urinary IL-10, serum CTLA-4, T-bet(+) , FoxP3(+) 
      change patterns and GATA3(+) /T-bet(+) ratio were significantly associated with 
      tumour recurrence (P = 0.001, P = 0.001, P = 0.02, P = 0.009 and P = 0.001, 
      respectively). Tumour progression occurred in 34 (18.3%) patients. Urinary IL-10, 
      serum CTLA-4, serum T-bet(+) change patterns and GATA3(+) /T-bet(+) ratio were 
      independent predictors of tumour progression (P = 0.001, P = 0.001, P = 0.02 and 
      P = 0.001, respectively). CONCLUSIONS: Urinary IL-10 and serum TNF-alpha can 
      significantly predict ICR. Moreover, change pattern of urinary IL-10, serum 
      CTLA-4, TFs (GATA3, T-bet and FoxP3) and GATA3(+) /T-bet(+) ratio after BCG 
      induction can independently predict further BCG response. These markers could be 
      implemented in clinical practice when management options are discussed or in 
      systems with severe BCG shortage.
CI  - (c) 2021 The Authors BJU International (c) 2021 BJU International.
FAU - Elsawy, Amr A
AU  - Elsawy AA
AUID- ORCID: 0000-0001-7077-8094
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Abol-Enein, Hassan
AU  - Abol-Enein H
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Laymon, Mahmoud
AU  - Laymon M
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Ahmed, Asmaa E
AU  - Ahmed AE
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Essam, Ahmed
AU  - Essam A
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Hamam, Eman T
AU  - Hamam ET
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Zidan, Abdel-Aziz A
AU  - Zidan AA
AD  - Department of Zoology, Faculty of Science, Damanhour University, Damanhour, 
      Egypt.
FAU - Zahran, Mohamed H
AU  - Zahran MH
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Shokeir, Ahmed A
AU  - Shokeir AA
AUID- ORCID: 0000-0003-2699-2629
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
FAU - Awadalla, Amira
AU  - Awadalla A
AD  - Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210913
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (BCG Vaccine)
RN  - 0 (Biomarkers)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adjuvants, Immunologic/therapeutic use
MH  - Administration, Intravesical
MH  - BCG Vaccine/therapeutic use
MH  - Biomarkers
MH  - CTLA-4 Antigen
MH  - Forkhead Transcription Factors/therapeutic use
MH  - Humans
MH  - Interleukin-10/therapeutic use
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Tumor Necrosis Factor-alpha
MH  - *Urinary Bladder Neoplasms/pathology
OTO - NOTNLM
OT  - T cells
OT  - bacille Calmette-Guerin response
OT  - bladder cancer
OT  - prediction
OT  - progression
OT  - recurrence
OT  - urinary cytokines
EDAT- 2021/08/28 06:00
MHDA- 2022/09/16 06:00
CRDT- 2021/08/27 08:44
PHST- 2021/08/09 00:00 [revised]
PHST- 2021/05/26 00:00 [received]
PHST- 2021/08/23 00:00 [accepted]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2022/09/16 06:00 [medline]
PHST- 2021/08/27 08:44 [entrez]
AID - 10.1111/bju.15582 [doi]
PST - ppublish
SO  - BJU Int. 2022 Oct;130(4):444-453. doi: 10.1111/bju.15582. Epub 2021 Sep 13.