Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A Short Report

Dorota Pawlik-Gwozdecka,Maciej Zieliński,Justyna Sakowska,Francesco Cappello,Piotr Trzonkowski,Maciej Niedźwiecki,Magdalena Górska-Ponikowska

doi:10.3390/app11167325

Abstract

HSPs demonstrate a strong association with gamma-delta (γδ) T cells. Most of the studies regarding interactions between the parameters were conducted in the 1990s. Despite promising results, the concept of targeting γδ T cells by HSPs seems to be a forgotten direction due to potent non-peptidic phosphoantigens rather than HSPs have been found to be the essential stimulatory components for human γδ cells. Currently, with greater knowledge of lymphocyte diversity, and more accurate diagnostic methods, we decided to study the correlation once again in the neoplastic condition. Twenty-one children with newly diagnosed acute lymphoblastic leukaemia (ALL) were enrolled on the study. Serum HSP90 concentrations were evaluated by an enzyme-linked immunosorbent assay (ELISA), subsets of γδ T cells (CD3+ γδ, CD3+ γδ HLA/DR+, CD4+ γδ and CD8+ γδ) by flow cytometry. We have shown statistically relevant correlations between serum HSP90 and CD3+ HLA/DR+ γδ T cells in paediatric ALL at diagnosis (R = 0.53, p < 0.05), but not after induction chemotherapy. We also have demonstrated decreased levels of both serum HSP90 and CD3+ HLA/DR+ γδ T cells before treatment, which may indirectly indicate dose-dependent unknown interaction between the parameters. The results of our study may be a good introduction to research on the association between HSPs and CD3+ HLA/DR+ γδ T cells, which could be an interesting direction for the development of anti-cancer strategies, not just for childhood ALL.

Highlights

Heat-shock proteins (HSPs) have recently been extensively studied in the context of anticancer properties, especially their extracellular form
Due to the limited reports concerning extracellular HSP90—one of the most investigated proteins of the HSP family and the correlation with the frequency of specific subunits of γδ T cells in cancers, we examined the relationship between these parameters in the peripheral blood of 21 paediatric patients with B-cell acute lymphoblastic leukaemia (ALL)—
We demonstrated no correlations between serum HSP90 and CD3+ γδ T cells before and after induction chemotherapy, CD4+ γδ Tcells and CD8+ γδ

Summary

Introduction

Heat-shock proteins (HSPs) have recently been extensively studied in the context of anticancer properties, especially their extracellular form. Serum HSPs have been found to elicit antitumour immunity by acting as tumour-specific antigens, and adjuvants that facilitate uptake, processing, and presentation [1,2]. Human γδ T cells represent a small subset of CD3+ T lymphocytes (1–10%), these cells have been gaining the interest of scientists’ and clinicians’ as they demonstrate both innate and adaptive immune properties. Their primary functions include phagocytosis and the presentation of soluble antigens to alpha-beta (αβ) T cells, induction of dendritic cells (DC), maturation and the production of cytokines [4]. The key advantage of γδ T cells is their ability to identify antigens out of the context of the classical major histocompatibility complex (MHC) and the natural tropism of γδ T cells for the tumour microenvironment [5]

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