Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer

Chen, Cheng; Chen, Zhijun; Chen, Dongdong; Zhang, Binjie; Wang, Zhaoye; Le, Hanh

doi:10.1177/0300060514561504

Cited by 35 publications

(30 citation statements)

References 34 publications

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“…Preclinical evidence indicates that cisplatin increases the infiltration and cytotoxic activity of CD8 + T cells [74][75][76]. In addition, cisplatin and gemcitabine have also been described as increasing PD-L1 expression [77,78] and reducing the abundance of MDSCs [75,[79][80][81], Treg [82,83] and macrophages [84]. Limited studies have evaluated the effects of cisplatin and gemcitabine on antitumor immunity in UC patients.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder

Wilpe

Gerretsen

Heijden

et al. 2020

Cancers

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The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8+ T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as a biomarker for the response to checkpoint inhibitors, there are some indications that high CD8+ T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder

Wilpe

Gerretsen

Heijden

et al. 2020

Cancers

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“…These include conventional chemotherapy, which affects Tregs together with other cell types, as well as other strategies aimed at Tregs directly, including the use of specific monoclonal antibodies for CD25 (a depleting antibody), CTLA4 (a blocking antibody), GITR (an agonistic antibody) and OX40 (an agonistic antibody) (1,3,4). However, many current immunotherapeutic strategies that target Tregs may have a negative effect on effector immune cells (3,5), which may result in the therapy being unsuccessful. If immunotherapy is to become a viable option in the treatment of cancer, immunotherapeutic strategies that target Tregs must also have a positive effect on effector cells, shifting the balance in favor of immunity.…”

Section: Cytokine-induced Killer Cell Therapy For Modulating Regulatomentioning

confidence: 99%

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have reported that regulatory T cells (Tregs), which are physiologically engaged in the maintenance of immunological self-tolerance, have a critical role in the regulation of the antitumor immune response. Targeting Tregs has the potential to augment cancer vaccine approaches. The current study therefore aimed to evaluate the role of cytokine-induced killer (CIK) cell infusion in modulating Tregs in patients with non-small cell lung cancer (NSCLC). A total of 15 patients with advanced NSCLC were treated by an infusion of CIK cells derived from autologous peripheral blood mononuclear cells (PBMCs). By using flow cytometry and liquid chip analysis, subsets of T cells and natural killer (NK) cells in peripheral blood, and plasma cytokine profiles in the treated patients, were analyzed at 2 and 4 weeks after CIK cell infusion. Cytotoxicity of PBMCs (n=15) and NK cells (n=6) isolated from NSCLC patients was evaluated before and after CIK cell therapy. Progression-free survival (PFS) and overall survival (OS) were also assessed. Analysis of the immune cell populations before and after treatment showed a significant increase in NK cells (P<0.05) concomitant with a significant decrease in Tregs (P<0.01) at 2 weeks post-infusion of CIK cells compared with the baseline. NK group 2D receptor (NKG2D) expression on NK cells was also significantly increased at 2 weeks post-infusion compared with the baseline (P<0.05). There was a positive correlation between NKG2D expression and the infusion number of CIK cells (P<0.05).

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“…However, the effect of gemcitabine on other T cell populations was not assessed in this study ( 158 ). Also, other (combinations of) chemotherapy drugs have been reported to influence the presence or function of T regs ( 159 , 160 ).…”

Section: Immunomodulatory Properties Of Chemotherapeutic Drugsmentioning

confidence: 99%

Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer Immunotherapy

2015

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Cancer immunotherapy is gaining momentum in the clinic. The current challenge is to understand why a proportion of cancer patients do not respond to cancer immunotherapy, and how this can be translated into the rational design of combinatorial cancer immunotherapy strategies aimed at maximizing success of immunotherapy. Here, we discuss how tumors orchestrate an immunosuppressive microenvironment, which contributes to their escape from immune attack. Relieving the immunosuppressive networks in cancer patients is an attractive strategy to extend the clinical success of cancer immunotherapy. Since the clinical availability of drugs specifically targeting immunosuppressive cells or mediators is still limited, an alternative strategy is to use conventional chemotherapy drugs with immunomodulatory properties to improve cancer immunotherapy. We summarize the preclinical and clinical studies that illustrate how the anti-tumor T cell response can be enhanced by chemotherapy-induced relief of immunosuppressive networks. Treatment strategies aimed at combining chemotherapy-induced relief of immunosuppression and T cell-boosting checkpoint inhibitors provide an attractive and clinically feasible approach to overcome intrinsic and acquired resistance to cancer immunotherapy, and to extend the clinical success of cancer immunotherapy.

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Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer

Cited by 35 publications

References 34 publications

Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder

Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder

Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer

Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer Immunotherapy

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