scholarly journals Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+T Lymphocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wanshuai Li ◽  
Yang Yang ◽  
Zijun Ouyang ◽  
Qi Zhang ◽  
Lu Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Lewis Lung ◽  
Lewis Lung Cancer ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
And Function

Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC) cells.Methods. LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days.Results. Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8+T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon-γ(ifn-γ), perforin-1 (prf-1), and granzyme B (gzmb) in CD8+T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin.In vitrostudies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels ofifn-γ,prf-1,andgzmbin CD8+T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8+T cells.Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8+T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China.

scholarly journals Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models

2018 ◽  
Vol Volume 11 ◽  
pp. 5133-5142 ◽  
Author(s):  
Xibing Zhuang ◽  
Tiankui Qiao ◽  
Sujuan Yuan ◽  
Qi Zhang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lewis Lung ◽  
Lewis Lung Cancer ◽  
Antitumor Effects ◽  
Cancer Models

Phenotypic and Functional Effects of Perifosine on Dendritic Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4803-4803
Author(s):  
Weihua Song ◽  
Teru Hideshima ◽  
Yu-Tzu Tai ◽  
Kenneth C. Anderson ◽  
Nikhil C. Munshi
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Annexin V ◽  
Antitumor Agent ◽  
Dependent Manner ◽  
Immune Functions ◽  
Akt Inhibitor ◽  
Antitumor Effects

Abstract Perifosine is a synthetic novel alkylphospholipid, a new class of antitumor agent which targets cell membranes and inhibits Akt activation. Perifosine inhibits multiple myeloma (MM) cell growth in vitro and in vivo mouse model. Currently perifosine is under the evaluation of phase II clinical trail in MM. Although perifosine has shown significant direct antitumor effects, its effect on immune system has not yet been clarified. The objective of this study is to evaluate the effects of perifosine on the activity of antigen presenting cells (APCs). Monocyte-derived dendritic cells (DCs) from normal human donors were used as the APCs, and mature DCs were obtained by the treatment of TNF-α and IL-1β. Perifosine was used at the concentrations of 2.5 uM, 5 uM and 10 uM for the treatment with DCs. We first evaluated the effect of perifosine on the survival of DCs. We observed that the perifosine treatment up to 48 hours had no effect on viability (>90%) of DCs, assessed by annexin V and PI staining. Alteration of phenotype by perifosine on DCs was further examined by flow cytometry. Our results demonstrated that with dose-dependent manner, perifosine led to a significant down-regulation of surface antigens on immature DCs at 24 and 48 hours, which associated to costimulation (CD40, CD80 and CD86), antigen presentation (HLA-ABC, HLA-DPQR) and maturation (CD83). However, we did not observed significant effect of perifosine on above surface markers on mature DCs. Since DCs play a crucial role on the regulation of Th1/Th2 immune responses by the production of IL-12, we next evaluated IL-12 secretion by DCs with and without perifosine treatment. Importantly, treatment with perifosine significantly decreased LPS-induced-IL-12 production, compared to untreated DCs (untrt vs. trt = 192.29 vs. 166.23 pg/ml (2.5uM), 111.19 pg/ml (5uM) and 44.886 pg/ml (10uM)) at 24 hours. To assess the effect of perifosine on DCs function on the regulation of T cell responses, we stimulated allogenic T cells with mature DCs with or without the pre-treatment of perifosine. The proliferation assay by 3H-TdR incorporation and IFN-γ production by ELISA indicated perifosine-treated DCs had no significant effect on the regulation of T cells function. Taken together, these results showed that DCs function are influenced by the treatment of perifosine. Our pre-clinical data therefore indicates the need to monitor immune functions in patients under the Akt inhibitor treatment.

scholarly journals Functional and Molecular Characterization of PD1+ Tumor-Infiltrating Lymphocytes From Lung Cancer Patients

2021 ◽  
Author(s):  
Jesse Lipp ◽  
Limei Wang ◽  
Nathalie Harrer ◽  
Stefan Mueller ◽  
Sabina Berezowska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Wnt Signaling ◽  
Cell Activation ◽  
Effector Function ◽  
Transcriptional Analysis ◽  
Molecular Profile ◽  
Dependent Manner

Abstract Background The majority of infiltrating T-cells (TILs) in lung cancer are contained in the memory compartment and overexpress PD1 and have been associated with dysfunction. Antibody-mediated cancer immunotherapy targets inhibitory surface molecules, such as PD1, PD-L1, and CTLA-4, aiming to re-invigorate dysfunctional T cells.Methods Using fluorescence-activated cell sorting (FACS), we purified CD45RO+ memory CD8+ and CD4+ TILs and their patient-matched non-tumor counterparts from treatment-naïve NSCLC patient biopsies to better evaluate the effect of PD1 expression on the functional and molecular profile of tumor-resident T cells. Moreover, we compared the functional, molecular, and clonal composition of TIL preparations after TCR-dependent in vitro expansion with their freshly isolated counterparts in matched patients.Results We show that PD1+CD8+ TILs have elevated expression of the transcriptional regulator ID3 and that the overall cytotoxic potential of CD8 T cells can be improved by knocking down ID3, defining it as a potential regulator of T cell effector function. PD1+CD4+ memory TILs remain functionally intact and despite overexpressing key transcriptional activators known to negatively regulate CD8 function such as TOX and TOX2, display transcriptional patterns consistent with both follicular helper and regulator function and robustly facilitate B cell activation and expansion in response to TCR-dependent stimulation. Furthermore, we show that expanding ex vivo-prepared TILs in vitro in a TCR-dependent manner broadly preserves their functionality with respect to tumor cell killing, expansion and activation of B cells, and TCR repertoire. Although purified PD1+CD8+ TILs generally maintain an exhausted phenotype upon expansion in vitro, transcriptional analysis reveals a downregulation of markers of T cell dysfunction, including the co-inhibitory molecules PD1 and CTLA-4 and the transcription factors ID3, TOX and TOX2, while genes involved in cell cycle and DNA repair are upregulated. We find reduced expression of WNT signaling components to be a hallmark of PD1+CD8+ exhausted T cells in vivo and in vitro and demonstrate that restoring WNT signaling, by pharmacological blockade of GSK3β, can improve effector function. Conclusions These data unveil novel targets for tumor immunotherapy and have promising implications for development of a personalized adoptive TIL-based cell therapy for lung cancer.

scholarly journals Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhuo Chen ◽  
Xiang Qian ◽  
Shasha Chen ◽  
Xiaoxuan Fu ◽  
Guanjun Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Therapeutic Efficacy ◽  
Combined Treatment ◽  
Receptor Interaction ◽  
Lewis Lung ◽  
Cancer Model ◽  
Lewis Lung Cancer ◽  
Antitumor Effects ◽  
Akkermansia Muciniphila ◽  
Lung Cancer Model

Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-γ, interleukin-6, and tumor necrosis factor-α, and suppressed the expression of CD4+CD25+Foxp3+ Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.

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