Mathieu Rouanne1, Reem Betari2, Camélia Radulescu3, Aïcha Goubar4, Nicolas Signolle5, Yann Neuzillet2, Yves Allory6, Aurélien Marabelle7, Julien Adam8, Thierry Lebret2. 1. INSERM Unit U1015, Laboratoire de Recherche Translationnelle en Immunothérapie, Gustave Roussy, Villejuif, France; Department of Urology, Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, Suresnes, France. Electronic address: mathieu.rouanne@gustaveroussy.fr. 2. Department of Urology, Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, Suresnes, France. 3. Department of Pathology, Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, Suresnes, France. 4. Department of Biostatistics, INSERM Unit U981, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. 5. Department of Experimental Pathology, INSERM Unit U981, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. 6. Department of Pathology, Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, Suresnes, France; Institut Curie, CNRS, UMR144, Paris, France. 7. INSERM Unit U1015, Laboratoire de Recherche Translationnelle en Immunothérapie, Gustave Roussy, Villejuif, France; Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. 8. Department of Biostatistics, INSERM Unit U981, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France; Department of Pathology, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
Abstract
INTRODUCTION: Assessment of tumour-infiltrating lymphocytes (TILs) can provide important prognostic information in various cancers and may be of value in predicting response to immunotherapy. The objective of the present study was to investigate the association of stromal lymphocytic infiltration with clinicopathological parameters and their correlation with outcomes in patients with high-grade pT1 non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively analysed clinical data and formalin-fixed paraffin-embedded (FFPE) tissues of 147 patients with primary high-grade pT1 NMIBC who underwent transurethral resection of the bladder. The stromal TIL density was scored as percentage of the stromal area infiltrated by mononuclear inflammatory cells over the total intratumoural stromal area. The main end-point was correlation with cancer-specific survival (CSS). RESULTS: Median follow-up was 8.2 years (6.1-9.5). Induction Bacillus Calmette-Guérin therapy was undergone by 126 patients (86%). Stromal TILs were high (≥10%) in 82 tumours (56%) and were positively associated with the tumour invasion depth (p = 0.01) and cancers with variant histology (p = 0.01). For the CSS analysis, high (≥10%) versus. low (<10%) stromal TIL hazard ratio (95% confidence interval) was 1.70 (0.7-3.9, p = 0.2). CONCLUSIONS: A higher density of stromal TILs was associated with the tumour invasion depth in pT1 NMIBC. The level of TILs was not associated with survival outcomes. These data suggest that tumour aggressiveness is associated with an increased adaptive immune response in pT1 NMIBC. Characterisation of T-cell subtypes along with B-cells may be critical to enhance our knowledge of the host immune response in patients with high-risk NMIBC.
INTRODUCTION: Assessment of tumour-infiltrating lymphocytes (TILs) can provide important prognostic information in various cancers and may be of value in predicting response to immunotherapy. The objective of the present study was to investigate the association of stromal lymphocytic infiltration with clinicopathological parameters and their correlation with outcomes in patients with high-grade pT1 non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively analysed clinical data and formalin-fixed paraffin-embedded (FFPE) tissues of 147 patients with primary high-grade pT1 NMIBC who underwent transurethral resection of the bladder. The stromal TIL density was scored as percentage of the stromal area infiltrated by mononuclear inflammatory cells over the total intratumoural stromal area. The main end-point was correlation with cancer-specific survival (CSS). RESULTS: Median follow-up was 8.2 years (6.1-9.5). Induction Bacillus Calmette-Guérin therapy was undergone by 126 patients (86%). Stromal TILs were high (≥10%) in 82 tumours (56%) and were positively associated with the tumour invasion depth (p = 0.01) and cancers with variant histology (p = 0.01). For the CSS analysis, high (≥10%) versus. low (<10%) stromal TIL hazard ratio (95% confidence interval) was 1.70 (0.7-3.9, p = 0.2). CONCLUSIONS: A higher density of stromal TILs was associated with the tumour invasion depth in pT1 NMIBC. The level of TILs was not associated with survival outcomes. These data suggest that tumour aggressiveness is associated with an increased adaptive immune response in pT1 NMIBC. Characterisation of T-cell subtypes along with B-cells may be critical to enhance our knowledge of the host immune response in patients with high-risk NMIBC.
Authors: Edward C Ottley; Robert Pell; Benedict Brazier; Julianne Hollidge; Christiana Kartsonaki; Lisa Browning; Eric O'Neill; Anne E Kiltie Journal: J Pathol Clin Res Date: 2020-05-06