PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: Associations with localized stage progression

Brant A. Inman, Thomas J. Sebo, Xavier Frigola, Haidong M Dong, Eric J. Bergstralh, Igor Frank, Yves Fradet, Louis Lacombe, Eugene D Kwon

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder. METHODS. Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment. RESULTS. PD-L1 expression was observed in 7% of pTa, 16% of pT1, 23% of pT2, 30% of pT3/4, and 45% of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P =.004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR = 4.77, 95% confidence interval [CI]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P =.012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment. CONCLUSIONS. Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.

Original languageEnglish (US)
Pages (from-to)1499-1505
Number of pages7
JournalCancer
Volume109
Issue number8
DOIs
StatePublished - Apr 15 2007

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CD80 Antigens
Mycobacterium bovis
Granuloma
Urinary Bladder
Carcinoma
Neoplasms
Odds Ratio
Pathology
T-Lymphocytes
Kidney Neoplasms
Membrane Glycoproteins
Carcinoma in Situ
Urinary Bladder Neoplasms
Immunotherapy

Keywords

  • BCG
  • Bladder cancer
  • Programmed death ligand-1
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata : Associations with localized stage progression. / Inman, Brant A.; Sebo, Thomas J.; Frigola, Xavier; Dong, Haidong M; Bergstralh, Eric J.; Frank, Igor; Fradet, Yves; Lacombe, Louis; Kwon, Eugene D.

In: Cancer, Vol. 109, No. 8, 15.04.2007, p. 1499-1505.

Research output: Contribution to journalArticle

Inman, Brant A. ; Sebo, Thomas J. ; Frigola, Xavier ; Dong, Haidong M ; Bergstralh, Eric J. ; Frank, Igor ; Fradet, Yves ; Lacombe, Louis ; Kwon, Eugene D. / PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata : Associations with localized stage progression. In: Cancer. 2007 ; Vol. 109, No. 8. pp. 1499-1505.
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abstract = "BACKGROUND. PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder. METHODS. Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment. RESULTS. PD-L1 expression was observed in 7{\%} of pTa, 16{\%} of pT1, 23{\%} of pT2, 30{\%} of pT3/4, and 45{\%} of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P =.004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR = 4.77, 95{\%} confidence interval [CI]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P =.012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment. CONCLUSIONS. Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.",
keywords = "BCG, Bladder cancer, Programmed death ligand-1, Urothelial carcinoma",
author = "Inman, {Brant A.} and Sebo, {Thomas J.} and Xavier Frigola and Dong, {Haidong M} and Bergstralh, {Eric J.} and Igor Frank and Yves Fradet and Louis Lacombe and Kwon, {Eugene D}",
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T1 - PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata

T2 - Associations with localized stage progression

AU - Inman, Brant A.

AU - Sebo, Thomas J.

AU - Frigola, Xavier

AU - Dong, Haidong M

AU - Bergstralh, Eric J.

AU - Frank, Igor

AU - Fradet, Yves

AU - Lacombe, Louis

AU - Kwon, Eugene D

PY - 2007/4/15

Y1 - 2007/4/15

N2 - BACKGROUND. PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder. METHODS. Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment. RESULTS. PD-L1 expression was observed in 7% of pTa, 16% of pT1, 23% of pT2, 30% of pT3/4, and 45% of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P =.004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR = 4.77, 95% confidence interval [CI]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P =.012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment. CONCLUSIONS. Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.

AB - BACKGROUND. PD-L1 (programmed death ligand 1, B7-H1) is a cell surface glycoprotein that can impair T-cell function. PD-L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD-L1 was evaluated as a mechanism for local stage progression in urothelial carcinoma (UC) of the bladder. METHODS. Using immunohistochemistry, PD-L1 expression was evaluated in a cohort of 280 high-risk UCs of the bladder. PD-L1 was modeled as a predictor of bladder cancer stage using ordinal logistic regression. Other covariates evaluated as potential confounders included age, gender, tumor grade, and lymphocytic infiltration. Further, PD-L1 was evaluated as a potential mechanism of bacillus Calmette-Guerin (BCG) failure in the subset of high-risk nonmuscle-invasive tumors that received this treatment. RESULTS. PD-L1 expression was observed in 7% of pTa, 16% of pT1, 23% of pT2, 30% of pT3/4, and 45% of carcinoma in situ (CIS) tumors. PD-L1 expression was associated with high-grade tumors (odds ratio [OR] = 2.4, P = .009) and tumor infiltration by mononuclear cells (OR = 5.5, P =.004). We observed that the key determinants of stage progression in this cohort were World Health Organization/International Society of Urologic Pathology (WHO/ISUP) high-grade tumor pathology (OR = 4.77, 95% confidence interval [CI]: 2.73-8.34; P < .001) and PD-L1 expression (OR = 2.20, P =.012). PD-L1 expression was found to be extremely abundant in the BCG-induced bladder granulomata in 11 of 12 patients failing BCG treatment. CONCLUSIONS. Collectively, these data indicate that tumor PD-L1 may facilitate localized stage-advancement of UC and attenuate responses to BCG immunotherapy by neutralizing T cells that normally guard against cancer invasion from the epithelium into the bladder musculature.

KW - BCG

KW - Bladder cancer

KW - Programmed death ligand-1

KW - Urothelial carcinoma

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