Investig Clin Urol.  2021 Jan;62(1):39-46. 10.4111/icu.20200116.

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

• Zhang L
• Zirakzadeh AA
• Rosvall J
• Hedlund M
• Hu PS
• Riklund K
• Sherif A
• Winqvist O

• KMID: 2509848
• DOI: http://doi.org/10.4111/icu.20200116

Abstract

Purpose
Nearly half of penile cancers are related to human papillomavirus (HPV) infection. Investigations of tumor- and HPVspecific 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%). Thus, 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.

Keyword

Adoptive immunity; Lymph node excision; Papillomaviridae; Penile neoplasms; T-lymphocytes