Abstract
The distribution and function of T lymphocytes in human lung cancer remain limited. In this study, we investigated the properties of human T cell subsets in the blood of non-small cell lung cancer (NSCLC) patients. We found a relatively normal level of CD4+ subsets in the blood of NSCLC patients, but CD8+ effector T cells increased and CD8+ effector memory cells declined compared to the healthy donors. To further analyze their properties, we stimulated the peripheral blood mononuclear cells (PBMCs) of NSCLC patients by mitogens to examine cytokine production. Our data suggest that both CD4+ and CD8+ naïve cells in NSCLC patients significantly reduced IFN-γ and TNF-α production. Additionally, fewer CD8+ effector cells produced IFN-γ and TNF-α in NSCLC patients than in healthy subjects. Moreover, similar results were observed for CD4+ or CD8+ memory cells in NSCLC patients for the production of IFN-γ, TNF-α, and IL-17. Therefore, our results strongly suggest that the function of CD4+ and CD8+ T lymphocytes in NSCLC patients is compromised or dysregulated. The development of vaccines and antitumor immunotherapy may be essential for the treatment of lung cancer patients.
Highlights
Immunological memory is critical for long-term immunity and protection from infection
To assess the distribution of the CD4+ and CD8+ T cell subsets in human lung cancer, we analyzed the Tn, Tcm, Tem, and Teff of the peripheral blood mononuclear cells (PBMCs) from the healthy donors and nonsmall cell lung cancer (NSCLC) patients by flow cytometry according to established surface markers (Tables 1 and 2) [1, 2]
We found that the frequency of CD8+ T cells increased in blood (p = 0.0002) and lymph node (p = 0.022) from NSCLC patients compared to the normal group, while the frequency of CD4+ T cells declined in NSCLC-Ly group (p = 0.022)
Summary
Immunological memory is critical for long-term immunity and protection from infection. Only a small fraction of effector T cells becomes long-lived memory T cell to provide lifelong protection against the previously encountered pathogens [2, 3]. Recent data revealed that adoptively transferred different subsets of memory T cells have different antitumor activity in mouse models [5]. The distribution and function of human memory T cells have been identified in healthy subjects [6], but the physiological distribution and function of human T cell subsets in lung cancer are still limited. The understanding of the compartmentalization of memory T cell subsets will provide valuable basis for designing tumor immunotherapy
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