Aim
To characterize immune suppression in lymphoma, thymocyte selection‐associated high mobility group box protein (TOX) expression and co‐expression with programmed cell death receptor‐1 (PD‐1), T cell immunoglobulin mucin‐domain‐containing‐3 (Tim‐3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed.
Methods
TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi‐color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals.
Results
An increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non‐Hodgkin's lymphoma (B‐NHL) in comparison with healthy controls. Moreover, TOX+PD‐1+ and TOX+Tim‐3+ double‐positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B‐NHL group. There was apparent heterogeneity in TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD‐1+ Treg cells also significantly increased in the B‐NHL group.
Conclusions
Higher expression of TOX concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with B‐NHL may contribute to T cell exhaustion and impair their special anti‐tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies.