Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients

Abstract

SummaryThe pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a doubleenzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 nonmalignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3z and CD3e was also determined. The prevalence of CD4 + FoxP3 + cells in CD4 + T cells and the ratio of FoxP3 + /CD8 + were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3 NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25 + FoxP3 -cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3 + /CD25 + FoxP3 -was found in non-keratinizing and undifferentiated carcinomas. Increased CD4 + FoxP3 + /CD4 + proportion and FoxP3 + /CD8 + ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3z in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.

The role of tumor cells in the modification of T lymphocytes activity — the expression of the early CD69⁺, CD71⁺ and the late CD25⁺, CD26⁺, HLA/DR⁺ activation markers on T CD4⁺ and CD8⁺ cells in squamous cell laryngeal carcinoma. Part I

“…This does not allow direct comparisons of results obtained in patients with laryngeal cancer [13,[22][23][24][25][26][27][28][29]. In addition, the findings show large discrepancies in the assessment of the T cells activity in various types of head and neck cancers, and lead to a different conclusion regarding the expression of activation markers on T lymphocytes in patients with neoplastic disease [22][23][24][25][26][27][28][29]. This indicates the necessity of an individual approach to the immunological phenomena observed in a particular type of cancer, in order to properly interpret the results.…”

“…Despite these limitations, studies on the pathogenesis and immunopathology of head and neck carcinomas clearly indicate the existence of complex disorders in the regulatory mechanisms of immune cellular response as well as the suppression and decreased activity of T cells in cancer patients [22][23][24][25][26][27][28][29]. One reason for the ineffectiveness of the mechanisms of immune cell response to tumor antigens may be the reduced rate and/or reduction in the number and activity of T CD4 + lymphocytes, also confirmed in this study, which has an impact on the function and activity of T CD8 + cells.…”

“…CD4 + T cells are important in preventing anergy of cytotoxic lymphocytes and are involved in the formation of memory CD8 + subpopulation, as well as stimulating macrophages and eosinophils present in the tumor stroma [30,31]. In light of the role of T CD4 + lymphocytes in the activation of antitumor mechanisms, reducing the activity of this subpopulation of T cells results in decreased activity and abnormal cytotoxic T CD8 + cell function, but also of other cells involved in immunological processes such as CD56 + NK cells and macrophages, actively involved in the cellular response [22][23][24][25][26][27][28][29]. Evidence of suppression of www.fhc.viamedica.pl the immune response and reduction in the cytotoxic activity of defense mechanisms directed against tumor antigens, is provided by the diminished expression of surface molecules (perforins, granzymes, FasL receptors) on CD8 + T cells and CD56 + NK cells confirmed in studies by other authors [22].…”

“…+ and CD8 + cells occurring in cancer patients, repopulation of lymphocytes from naïve cells as well as the immune response determined by the activity of memory cells are the resultant of immune mechanisms in cancer disease [8,12,23,24,28]. A detailed assessment of T CD4 + and CD8 + lymphocytes, including memory cells, naïve cells and Treg lymphocytes, was not analyzed in the studied group of squamous cell carcinoma of the larynx.…”

Prognostic value of the immunological phenomena and relationship with clinicopathological characteristics of the tumor — the expression of the early CD69⁺, CD71⁺and the late CD25⁺, CD26⁺, HLA/DR ⁺ activation markers on T CD4⁺ and CD8⁺ lymphocytes in squamous cell laryngeal carcinoma. Part II

“…In the literature concerning this subject, many researchers have pointed to the important role of immune system disturbances in cancer patients [1][2][3][4][5][6][7]. In recent years, various research centers have performed multi-experimental and clinical studies on the regulatory mechanisms that determine the activity of immune system cells in response to tumor cells of different origins.…”