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Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
Sundsvall Hosp, Sweden; Umea Univ, Sweden.
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2018 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, no 6, p. 688-692Article in journal (Refereed) Published
Abstract [en]

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. Patient summary: 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. (C) 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2018. Vol. 74, no 6, p. 688-692
Keywords [en]
Chemotherapy; Sentinel node; T cells; Urothelial bladder cancer
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-153150DOI: 10.1016/j.eururo.2018.06.048ISI: 000450121100008PubMedID: 30025882OAI: oai:DiVA.org:liu-153150DiVA, id: diva2:1267339
Note

Funding Agencies|Swedish Cancer Foundation; Wallenberg Foundation; Swedish Medical Research Council, Vinnova; Regionala forskningsradet in Uppsala-Orebroregionen (RFR in Uppsala-Orebro); Swedish Research Council; Cancer Research Foundation in Norrland, Umea, Sweden; Karolinska Research Network Program in Immune Modulatory Therapies for Autoimmunity and Cancer

Available from: 2018-12-01 Created: 2018-12-01 Last updated: 2019-04-12

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Huge, YlvaAljabery, FirasSherif, Amir
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Department of Clinical and Experimental MedicineFaculty of Medicine and Health SciencesDepartment of Urology in Östergötland
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