Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8+ effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4+ Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs.
In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.
European urology. 2018 Jul 16 [Epub ahead of print]
David Krantz, Ciputra Adijaya Hartana, Malin E Winerdal, Markus Johansson, Farhood Alamdari, Tomasz Jakubczyk, Ylva Huge, Firas Aljabery, Karin Palmqvist, A Ali Zirakzadeh, Benny Holmström, Katrine Riklund, Amir Sherif, Ola Winqvist
Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden., Department of Urology, Sundsvall Hospital, Sundsvall, Sweden; Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden., Department of Urology, Västmanland Hospital, Västerås, Sweden., Department of Urology, Ryhov County Hospital, Jönköping, Sweden., Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden., Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; Urology Section, Department of Surgery, Östersund County Hospital, Östersund, Sweden., Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden., Department of Urology, Akademiska University Hospital, Uppsala, Sweden., Department of Radiation Sciences, Diagnostics Radiology, Umeå University, Umeå, Sweden., Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden., Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: .