Investigative and Clinical Urology (Jan 2021)

Immune responses against autologous tumor and human papilloma virus in lymph nodes from patients with penile cancer

  • Lu Zhang,
  • A. Ali Zirakzadeh ,
  • Jesper Rosvall ,
  • Mats Hedlund ,
  • Ping Sheng Hu ,
  • Katrine Riklund ,
  • Amir Sherif ,
  • Ola Winqvist

DOI
https://doi.org/10.4111/icu.20200116
Journal volume & issue
Vol. 62, no. 1
pp. 39 – 46

Abstract

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Purpose: Nearly half of penile cancers are related to human papillomavirus (HPV) infection. Investigations of tumor- and HPV-specific T cell reactivity in regional lymph nodes (LNs) from patients with penile cancer are warranted. Materials and Methods: In this study, single-cell suspensions from LNs and peripheral blood from 11 patients with penile cancer were stained with antibodies for lymphocyte markers and analyzed by fluorescence-activated cell sorting (FACS). DNA was extracted from the tumor tissue and HPV status was investigated by PCR. Results: T-cell reactivity against autologous tumor-extract and against the HPV-vaccine Gardasil® was tested by flow-cytometric assay of specific cell-mediated immune response in activated whole blood (FASCIA). CD4+/CD8+ ratios were significantly lower in HPV positive LNs (p<0.05). Immune responses to tumor extract assessed by blast transformation and expansion in vitro, of either CD4+ or CD8+ T-cells, were found in 9 of 13 LNs (69%). 5 of 6 tested patients demonstrated T cell recognition of tumor-associated antigen(s). In HPV-positive patients, dose-dependent T cell responses against L1 (late) HPV proteins (Gardasil vaccine) were demonstrated. Conclusions: LN-derived T cells from patients with penile cancer recognize tumor antigen(s) and in HPV-positive cases, there is a response against L1 (late) HPV proteins, being constituents of the Gardasil vaccine.

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