Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 6/2019

17.04.2019 | Original Article

Age and sex have no impact on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy

verfasst von: Bradley C. Holland, Akshay Sood, Kristin Delfino, Danuta I. Dynda, Sophia Ran, Natalie Freed, Shaheen Alanee

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Advanced age and female sex have been associated with worse outcomes in patients undergoing radical cystectomy for muscle-invasive bladder cancer. A reduced immune response has been implicated as a mechanism. The objective of our study was to analyze the expression patterns of various cellular proteins active in bladder cancer immune pathways, and assess the correlation between age, sex, and the expression of these immune markers.

Methods

We obtained surgical tissue samples from equally distributed male/female patients with/without lymph node metastasis who had undergone radical cystectomy for urothelial carcinoma (UC) of the bladder (n = 50). Immunohistochemistry (IHC) for CD3 (cluster of differentiation), CD4, CD8, CD56, LAG-3 (lymphocyte-activation gene), TIM-3 (T-cell immunoglobulin and mucin-domain), PD-1 (programmed death) and PD-L1 molecules was performed and scored by a single pathologist (high versus low). Spearman’s correlation and Chi square tests investigated the association between age, sex, and IHC results.

Results

Mean age at surgery was 67 years (range 50–78 years); all patients were Caucasians. The following percent of patients scored high for a stain: 18% CD3, 10% CD4, 0% CD8, 0% CD56, 20% LAG-3, 4% TIM-3, 0% PD-1 and 0% PD-L1. There was no association between patients’ age, sex, and the expression of any of the immune markers (p > 0.05 for all).

Conclusions

The association between advanced age, female sex, and worse outcomes in bladder cancer may be independent of the immune pathways active in the disease that we examined in this study.
Literatur
2.
Zurück zum Zitat Messer JC, Shariat SF, Dinney CP et al (2014) Female gender is associated with a worse survival after radical cystectomy for urothelial carcinoma of the bladder: a competing risk analysis. Urology 83:863CrossRefPubMed Messer JC, Shariat SF, Dinney CP et al (2014) Female gender is associated with a worse survival after radical cystectomy for urothelial carcinoma of the bladder: a competing risk analysis. Urology 83:863CrossRefPubMed
3.
Zurück zum Zitat Zeegers MP, Tan FE, Dorant E et al (2000) The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer 89:630CrossRefPubMed Zeegers MP, Tan FE, Dorant E et al (2000) The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer 89:630CrossRefPubMed
4.
Zurück zum Zitat Lucca I, Fajkovic H, Klatte T (2014) Sex steroids and gender differences in nonmuscle invasive bladder cancer. Curr Opin Urol 24:500CrossRefPubMed Lucca I, Fajkovic H, Klatte T (2014) Sex steroids and gender differences in nonmuscle invasive bladder cancer. Curr Opin Urol 24:500CrossRefPubMed
6.
Zurück zum Zitat Chan ES, Yip SK, Hou SM et al (2013) Age, tumour stage, and preoperative serum albumin level are independent predictors of mortality after radical cystectomy for treatment of bladder cancer in Hong Kong Chinese. Hong Kong Med J 19:400CrossRefPubMed Chan ES, Yip SK, Hou SM et al (2013) Age, tumour stage, and preoperative serum albumin level are independent predictors of mortality after radical cystectomy for treatment of bladder cancer in Hong Kong Chinese. Hong Kong Med J 19:400CrossRefPubMed
7.
Zurück zum Zitat Shariat SF, Sfakianos JP, Droller MJ et al (2010) The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 105:300CrossRefPubMed Shariat SF, Sfakianos JP, Droller MJ et al (2010) The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 105:300CrossRefPubMed
8.
Zurück zum Zitat Paiola M, Knigge T, Duflot A et al (2018) Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates? Dev Comp Immunol 84:48CrossRefPubMed Paiola M, Knigge T, Duflot A et al (2018) Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates? Dev Comp Immunol 84:48CrossRefPubMed
9.
Zurück zum Zitat Sundahl N, Rottey S, De Maeseneer D et al (2018) Pembrolizumab for the treatment of bladder cancer. Expert Rev Anticancer Ther 18:107CrossRefPubMed Sundahl N, Rottey S, De Maeseneer D et al (2018) Pembrolizumab for the treatment of bladder cancer. Expert Rev Anticancer Ther 18:107CrossRefPubMed
10.
Zurück zum Zitat Massari F, Di Nunno V, Cubelli M et al (2018) Immune checkpoint inhibitors for metastatic bladder cancer. Cancer Treat Rev 64:11CrossRefPubMed Massari F, Di Nunno V, Cubelli M et al (2018) Immune checkpoint inhibitors for metastatic bladder cancer. Cancer Treat Rev 64:11CrossRefPubMed
11.
Zurück zum Zitat Udall M, Rizzo M, Kenny J et al (2018) PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol 13:12CrossRefPubMedPubMedCentral Udall M, Rizzo M, Kenny J et al (2018) PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol 13:12CrossRefPubMedPubMedCentral
12.
13.
Zurück zum Zitat Tracey E, Watt H, Currow D et al (2014) Investigation of poorer bladder cancer survival in women in NSW, Australia: a data linkage study. BJU Int 113:437CrossRefPubMed Tracey E, Watt H, Currow D et al (2014) Investigation of poorer bladder cancer survival in women in NSW, Australia: a data linkage study. BJU Int 113:437CrossRefPubMed
14.
Zurück zum Zitat Keller J, Chiou HY, Lin HC (2013) Increased risk of bladder cancer following diagnosis with bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 32:58CrossRefPubMed Keller J, Chiou HY, Lin HC (2013) Increased risk of bladder cancer following diagnosis with bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 32:58CrossRefPubMed
15.
Zurück zum Zitat Takahashi Y, Horio H, Hato T et al (2015) Prognostic significance of preoperative neutrophil-lymphocyte ratios in patients with stage I non-small cell lung cancer after complete resection. Ann Surg Oncol 22(Suppl 3):S1324CrossRefPubMed Takahashi Y, Horio H, Hato T et al (2015) Prognostic significance of preoperative neutrophil-lymphocyte ratios in patients with stage I non-small cell lung cancer after complete resection. Ann Surg Oncol 22(Suppl 3):S1324CrossRefPubMed
16.
Zurück zum Zitat Proctor MJ, McMillan DC, Morrison DS et al (2012) A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer 107:695CrossRefPubMedPubMedCentral Proctor MJ, McMillan DC, Morrison DS et al (2012) A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer 107:695CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Giefing-Kroll C, Berger P, Lepperdinger G et al (2015) How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14:309CrossRefPubMedPubMedCentral Giefing-Kroll C, Berger P, Lepperdinger G et al (2015) How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14:309CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Zhang L, Du H, Xiao TW et al (2015) Prognostic value of PD-1 and TIM-3 on CD3 + T cells from diffuse large B-cell lymphoma. Biomed Pharmacother 75:83CrossRefPubMed Zhang L, Du H, Xiao TW et al (2015) Prognostic value of PD-1 and TIM-3 on CD3 + T cells from diffuse large B-cell lymphoma. Biomed Pharmacother 75:83CrossRefPubMed
19.
Zurück zum Zitat Xu LY, Chen DD, He JY et al (2014) Tim-3 expression by peripheral natural killer cells and natural killer T cells increases in patients with lung cancer–reduction after surgical resection. Asian Pac J Cancer Prev 15:9945CrossRefPubMed Xu LY, Chen DD, He JY et al (2014) Tim-3 expression by peripheral natural killer cells and natural killer T cells increases in patients with lung cancer–reduction after surgical resection. Asian Pac J Cancer Prev 15:9945CrossRefPubMed
20.
Zurück zum Zitat Wu X, Zhang H, Xing Q et al (2014) PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients. Br J Cancer 111:1391CrossRefPubMedPubMedCentral Wu X, Zhang H, Xing Q et al (2014) PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients. Br J Cancer 111:1391CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Shi F, Shi M, Zeng Z et al (2011) PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer 128:887CrossRefPubMed Shi F, Shi M, Zeng Z et al (2011) PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer 128:887CrossRefPubMed
Metadaten
Titel
Age and sex have no impact on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy
verfasst von
Bradley C. Holland
Akshay Sood
Kristin Delfino
Danuta I. Dynda
Sophia Ran
Natalie Freed
Shaheen Alanee
Publikationsdatum
17.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-019-02340-w

Weitere Artikel der Ausgabe 6/2019

Cancer Immunology, Immunotherapy 6/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.