T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept

Abstract

ObjectiveTo define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration.MethodsA total of 252 patients underwent primary transurethral resection of bladder tumour at our Institution. A retrospective review of a selected cohort with pT1 and muscle-invasive bladder cancer (MIBC) lesions was performed. Pathology blocks were marked with CD3 and CD8 antibodies. Immune cells density in stromal reaction (SR) was measured on five distinct high-power field (HPF) by two dedicated uro-pathologist blinded for patients’ evolution.StatisticsStudent test or non-parametric Wilcoxon test as appropriate to compare means between two groups. Receiver operating characteristics (ROC) curve to define markers threshold. Cox model to assess survival’s predictors.ResultsTen pT1 and 20 MIBC consecutive cases were analysed. Median follow-up was 33.4 months. Immunohistological analysis for pT1 lesions featured limited SR. For MIBC, the mean density of lymphocytes in the SR was of 105/HPF (CD3) and 86/HPF (CD8). Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279). CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses. The retrospective design and small size of cohorts are the study limitations.ConclusionsHigh CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC. Th1 reaction against the tumour seems to be protective for bladder cancer. Further evaluation is warranted.

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

“…2). The majority support a positive impact on prognosis associated with extensive memory T-cell infiltration in the same cancers we discussed earlier, eg, CRC (Anitei et al, 2014;Boissi ere-Michot et al, 2014;Correale et al, 2012;Kim, Bae, et al, 2015;Ling et al, 2014;Ong et al, 2015;Shinto et al, 2014), bladder (Ingels et al, 2014), breast de Kruijf et al, 2013;García-Martínez et al, 2014;Kim et al, 2013;Mohammed et al, 2013;Park et al, 2012;Rathore et al, 2014;Seo et al, 2013;West et al, 2013), Merkel cell carcinoma (Paulson et al, 2014), glioma (Han et al, 2014), pancreatic (Ino et al, 2013;Tang et al, 2014), head and neck (Balermpas et al, 2014;Czystowska et al, 2013;Millrud et al, 2012;Wallis et al, 2015), cervical (Origoni et al, 2013), NSCLC Hald et al, 2013), gastric Feichtenbeiner et al, 2014;Kim et al, 2014), ovarian (Bachmayr-Heyda et al, 2013;Nielsen et al, 2012;Preston et al, 2013), and HCC (Cariani et al, 2012;Chen et al, 2012;Guo et al, 2007;Huang et al, 2012) (Table 1 and Fig. 2).…”

Cancer: A disease at the crossroads of trade‐offs

“…The helper T lymphocytes may have a central role for understanding the link between infections and cancer dynamics. In fact, several studies have shown that Th1 response is protective against several cancers (Haabeth et al., ; Ingels et al., ) and intracellular pathogens. In contrast, Th2 activation is linked to negative prognosis in some cancers (Lippitz, ) and it confers protection against macroparasites.…”

Infections and cancer: the “fifty shades of immunity” hypothesis

“…Such Th1-polarized lymphocytes activate cytotoxic T cells and macrophages which in turn destroy cancer cells. In agreement with this, a Th1-polarized response has been mainly recognized to be protective against several cancers [13, 14]. Finally, to avoid auto-immunity and chronic inflammation regulatory T cells (Treg) and other immunosuppressive cells are recruited at the tumor site.…”