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Background: Altered expression of T cell immune inhibitory receptors may result in immunosuppression and associate with the poor prognosis of leukemia patients in which the leukemic bone marrow (BM) microenvironment may contribute to such immunosuppression. We found higher numbers of programmed death-1 (PD-1) + exhausted T cells in peripheral blood (PB) from acute myeloid leukemia (AML) patients. To investigate the leukemic BM influence on immunosuppression, we further compared the distributions of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) and the exhausted T cell phenotype in PB and BM from AML patients and characterized their relationship with clinical outcome. Methods: PB and BM samples from 15 patients with newly diagnosed AML were collected and analyzed for the expression of PD-1, Tim-3, CD244, and CD57 on CD3+, CD4+, and CD8+ T cells by multicolor flow cytometry. Results: The proportions of PD-1 + CD3+ and PD-1 + CD8+ T cells were significantly higher in BM compared with PB. Similarly, higher PD-1 + CD244 + CD3+ and PD-1 + CD244 + CD8+ T cells were found in BM, and an increased tendency for PD-1 + CD244 + CD4+ T cells was also detected in this group. In contrast, increased Tim-3 + CD4+/ Tim-3 + CD244 + CD4+ T cells were predominant in BM compared with PB, but there was no statistically significant difference in Tim-3 + CD8+ T cells. Moreover, PD-1 and Tim-3 double-positive CD3+/CD4+/CD8+ T cells were significantly increased in the BM group. In addition, a higher proportion of PD-1 + Tim-3 + CD3+ T cells in the BM and PD-1 + Tim-3 + CD4+ T cells in PB was detected in non-complete remission (NCR) compared with complete remission (CR) patients after first-cycle chemotherapy. Conclusions: Upregulation of PD-1 and Tim-3 and the exhausted phenotype of CD4+ and CD8+ T cells in the BM of AML patients may contribute to mediating the leukemic immunosuppressive microenvironment, and increased PD-1 + Tim-3+ CD8+ T cells may be related to T cell dysfunction in AML, which may influence clinical outcome.

What is known and objective: Capsaicin, the major active ingredient of chili pepper, may play a "dual role" in tumourigenesis, acting as a carcinogen or as a cancer preventive agent. The aim of this study was to investigate the anticancer mechanisms of capsaicin and the effects of capsaicin on traditional chemotherapeutic drugs and radiotherapy in various cancer types and the potential for clinical application in cancer therapy. Methods: We conducted extensive literature searches through PubMed to collect representative studies of capsaicin in different cancer types. These studies investigated the anticancer molecular mechanisms of capsaicin.

We characterized the distribution of PD-1 and TIM-3 concurrent with exhausted CD3 , CD4 and CD8 T cells between BM and PB from patients with MM. Higher numbers of PD-1 CD244 or PD-1 CD57 CD3 T cells in BM from patients with MM may contribute to mediate the BM immunosuppressive microenvironment. Although heterogeneous alterations in Tim-3 T cells may represent a complex immunosuppressive pattern in MM. Overall, higher levels of PD-1 CD244 or PD-1/Tim-3 CD57 CD8 T cells may be a major reason for lower T-cell activation and T-cell immunodeficiency in MM.

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The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global T cell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR Vβ subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+T cells were increased in AML, particularly TCR Vβ2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death‐1 (PD‐1)+T cells in TCR Vβ subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD‐1+Vβ+T cells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD‐1+Vβ2+T cells with a high number of Vβ2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD‐1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+T cells were distributed in the AML‐M5 subtype group compared with the AML‐M3 group. In addition, higher PD‐1+ Vβ5.2+ and PD‐1+ Vβ12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD‐1+Vβ+T cells is a common characteristic of AML, higher PD‐1+Vβ2+T cells may be associated with a low antileukemia effect, and higher PD‐1+Vβ5.2+ and PD‐1+Vβ12+CD8+T cells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.

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Aim:To characterize the distribution of T cell immunoglobulin mucin-domain-containing-3 (Tim-3) within the exhausted T cells in patients with newly diagnosed acute myeloid leukemia (AML) and AML in complete remission. Methods:Tim-3 expression and coexpression with PD-1, CD244, and CD57 in CD3+, CD4+, and CD8+T cells were analyzed by multicolored fluorescent flow cytometry in peripheral blood from 28 newly diagnosed, untreated AML patient and 12 cases with AML in complete remission, 23 healthy individuals served as control.Results: Increasing Tim-3+CD244+ and Tim-3+CD57+ in CD3+, CD4+, and CD8+ T cells were found in AML and AML-CR groups in comparison with healthy controls. Similarly, increasing Tim-3 coexpression PD-1+ CD3+/CD4+/CD8+ T cells were found in AML group. A high tendency of PD-1+Tim-3+CD3+/CD4+/CD8+ T cells was detected in the AML-M4 subtype group followed by the M2 group, and a low tendency was found in the M3 group. Moreover, Tim-3+CD244+CD8+ T cells were found to be significantly higher in the M4 than that in M3 group. Dynamic changes of Tim-3+ T cells in AML patients who achieved CR after chemotherapy at different time points showed that Tim-3+ T cell subsets were evidently decreased; however, they remained at a higher level in most AML-CR patients.