The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer

Horn, Thomas; Laus, José Luis; Seitz, Anna Katharina; Maurer, Tobias; Schmid, Sebastian; Wolf, Petra; Haller, Bernhard; Winkler, Maximilian; Retz, Margitta; Nawroth, Roman; Gschwend, J. E.; Kübler, Hubert; Slotta‐Huspenina, Julia

doi:10.1007/s00345-015-1615-3

Cited by 87 publications

(86 citation statements)

References 21 publications

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“…An increased frequency of intratumoral FOXP3+ Tregs and inhibitory cytokines such as IL-10 and TGF-β was noted in bladder cancer patients compared to the healthy population [12, 22–23, 39]. Interestingly, Treg frequencies and CD25 high and FOXP3- cells in peripheral blood were similar in different patient groups (control group, localized BCa, lymphogen metastatic BCa and distant metastatic BCa).…”

Section: Discussionmentioning

confidence: 99%

“…In muscle-invasive bladder cancer, patients with FOXP3 expression in tumor cells had reduced long-term survival compared to patients with FOXP3-negative cancers [22]. Horn et al (2015) showed that a high FOXP3/CD8 ratio within invasive cancer tissue was an independent predictor of poor overall survival after cystectomy [23]. High numbers of CD68+ TAMs were associated with an advanced pT category and high-grade cancer [24], acting as an additional independent factor (CD68/CD3 ratio > 1) with a more than 7-fold higher risk of cancer-specific death on multivariate analysis [25].…”

Section: Discussionmentioning

confidence: 99%

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Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

et al. 2016

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Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25). Cell densities in the lamina propria without invasion, at the invasive front if present, in the papillary tumor stroma, and in the neoplastic urothelium were calculated. Twenty-nine (72.5%) of 40 patients were classified as BCG responders after a mean follow-up of 35.3 months. A statistically significant association was observed for BCG failure with low density of CD4+ and GATA3+ T-cells, and increased expression of FOXP3+ and CD25+ regulatory T-cells (Tregs) as well as CD68+ and CD163+ TAMs. Survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with an increased count of CD4+ and GATA3+ T-cells. TAMs, Tregs and T-bet+ T-cells were inversely correlated with RFS. Thus, the tumor microenvironment seems to influence the therapeutic response to BCG, permitting an individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

et al. 2016

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“…In muscle-invasive bladder cancer, specifically, the presence of CD8 + tumor-infiltrating lymphocytes (TILs) (18) and a low ratio of FOXP3 to CD4 or CD8 expression on TILs (19) have been associated with improved disease-free and overall survival rates. In keeping with the work by Sharma et al (18), Cox proportional hazards (Cox PH) modeling for each immune gene signature across all tumors in TCGA BLCA data set The box plots denote the interquartile range (IQR), with the box representing Q1 to Q3, the line denoting Q2, and the whiskers extending an additional 1.5 times the IQR beyond Q1 and Q3.…”

Section: Resultsmentioning

confidence: 99%

Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

Kardos¹,

Chai²,

Mose³

et al. 2016

JCI Insight

190

194

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“…In contrast, others have reported that CD3 + and CD8 + TILs are predictive of disease recurrence in patients with solitary low grade non-muscle invasive urothelial carcinoma and that CD4 + T cells are associated with a poor prognosis in this setting [257,258]. Another study showed that high CD3 + and CD8 + T cell infiltrates demonstrated trends towards better prognosis, but that high FOXP3/CD3 and FOXP3/CD8 ratios were correlated with poor outcomes [259]. Similar observations were made by Parodi and coworkers, who reported that the intra-tumoral T effector/T reg cell ratio in urothelial carcinoma patients with disease recurrence is invariably less than one, while it is always greater than one in patients without recurrence [260].…”

Section: Tils In Genitourinary Carcinomasmentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

611

366

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer

Cited by 87 publications

References 21 publications

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer

Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

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