scholarly journals The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Bin Wang ◽  
Jin Huang ◽  
Shanshan Li ◽  
Zhanyu Pan ◽  
Yongming Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Lewis Lung ◽  
Vascular Normalization ◽  
Immune Microenvironment ◽  
Lewis Lung Cancer ◽  
Combinatorial Therapy

Objective. As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment. Methods. Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining. Results. Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4+ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8+ cytotoxic T cells (CTLs), CD4+T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF. Conclusions. Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.

scholarly journals Ultrasound-Targeted Microbubble Destruction Alleviates Immunosuppression Induced by CD71+ Erythroid Progenitor Cells and Promotes PDL-1 Blockade Immunotherapy in the Lewis Lung Cancer Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Xi Tan ◽  
Cuo Yi ◽  
Yi Zhang ◽  
Najiao Tang ◽  
Yali Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Progenitor Cells ◽  
Tumor Control ◽  
Lewis Lung ◽  
Lewis Lung Cancer ◽  
Erythroid Progenitor ◽  
Invasive Approach ◽  
Erythroid Progenitor Cells

The CD71+ erythroid progenitor cells (CECs) exhibit distinctive immunosuppressive properties and regulate antitumor immunity to enable tumor growth. We presented a novel and non-invasive approach to improving immunity by targeting the splenic CECs via sonoporation generated by ultrasound-targeted microbubble destruction (UTMD). The systematic immunity enhanced by the reduction of PDL-1-expressing CECs also benefits the PDL-1 blockade therapy. In the Lewis lung cancer (LLC) model, the study group was treated by UTMD for 10 min at the splenic area with or without anti-mouse PDL-1 intraperitoneal injection. The frequency of splenic CEC, lymphocyte, and cytokine production was analyzed by flow cytometry. Serum interleukin-2 (IL-2) was tested by ELISA. Tumor volume was evaluated by two-dimensional ultrasound. The UTMD treatment consisted of ultrasound sonication and Sonazoid™ microbubble injection through the caudal vein. The mechanic index (MI) of ultrasound was set between 0.98 and 1.03. The results showed a significant reduction of splenic CECs and increased frequency of CD8+ T cells treated by UTMD treatment in the late-stage tumor. Tumor growth could be inhibited by UTMD combined with PDL-1 blockade therapy. The frequencies of interferon-γ (IFN-γ) producing CD8+ and CD4+ T cells were significantly increased after being treated by the combination of UTMD and PDL-1 blockade, while the reactive oxygen species (ROS) production and the fraction of the TGF-β-producing CD11b+ cells were significantly decreased. These preliminary findings suggest that UTMD enhances immune response and facilitates PDL-1 blockade therapy by targeting immunosuppressive CECs in the spleen. Our study provides new aspects and possibilities for treating cancer-related infection and tumor control in oncology.

Interleukin-18 suppresses tumor growth and induces tumor cells apoptosis on implanted Lewis lung cancer

2010 ◽  
Vol 9 (3) ◽  
pp. 142-144
Author(s):  
Sheng Yang ◽  
Huishan Lu ◽  
Xiangqi Chen ◽  
Tingyan Lin ◽  
Zhiying Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Lewis Lung ◽  
Interleukin 18 ◽  
Lewis Lung Cancer

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 IMMU-48. CD4+ T CELLS RESTRICT MEDULLOBLASTOMA GROWTH AND DISSEMINATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii115-ii115
Author(s):  
Tanja Eisemann ◽  
Robert Wechsler-Reya
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Cell Depletion ◽  
Immune Microenvironment ◽  
T Cell Depletion ◽  
Tumor Growth And Metastasis

Abstract The immune system serves as a powerful defense not only against pathogens and parasites but also against neoplastic cells. Emerging immunotherapies that boost the activity of tumor-reactive immune cells or counteract immune suppressive mechanisms have shown promising effects in certain types of cancer. However, the success of immunotherapy for brain tumors has been limited, highlighting the need for a better understanding of the immune microenvironment in these tumors. Our previous studies have shown that T cells critically affect growth of the pediatric brain tumor medulloblastoma. In particular, depletion of CD4+ T cells results in more aggressive growth of medulloblastoma cells and allows these cells to metastasize to the spinal cord. The anti-tumoral effects of CD4+ T cells are not due to their function as helpers for CD8+ cytotoxic T cells, since CD8+ T cell depletion did not enhance tumor growth to the same extent as CD4+ T cell depletion. To test whether CD4+ T cells can recognize MHC class II molecules on tumor cells and attack these cells directly, we generated tumors from MHC class II knockout mice. Surprisingly, depletion of CD4+ cells in these animals still enhanced tumor growth and metastasis. These results suggest that CD4+ T cells regulate medulloblastoma growth and metastasis in a manner that is independent of CD8+ T cells and independent of MHC-II on tumor cells. Ongoing studies are aimed at elucidating the mechanisms by which CD4+ T cells regulate medulloblastoma growth, including the antigen-presenting cells that activate them and the effector cells responsible for killing tumor cells following their activation. These studies will advance our understanding of the immune microenvironment in medulloblastoma and allow us to design more effective therapies for controlling tumor growth and metastasis.

Hirsutella sinensis Inhibits Lewis Lung Cancer via Tumor Microenvironment Effector T Cells in Mice

2018 ◽  
Vol 46 (04) ◽  
pp. 911-922 ◽  
Author(s):  
Huiying Fu ◽  
Lu Jin ◽  
Xia Shao ◽  
Yuanyuan Li ◽  
Fangming Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Suppressor Cell ◽  
Cordyceps Sinensis ◽  
Lewis Lung ◽  
Survival Times ◽  
Lewis Lung Cancer

Hirsutella sinensis fungus (HSF) is an artificial substitute of the well-known medicine Cordyceps sinensis with similar beneficial effects in humans. We previously found that HSF can regulate immune function and inhibit tumor growth; however, the mechanisms involved in these effects were still unclear. Accordingly, in this study, we investigated the effects of HSF on immune cell subsets in the tumor microenvironment in mice. The results showed that HSF inhibited Lewis lung cancer growth, alleviated abnormalities in routine blood tests, and enhanced tumor-infiltrating T cells, particularly the proportion of effector CD8[Formula: see text] T cells. In addition, HSF also ameliorated the immune-suppressive microenvironment and decreased the proportions of regulatory T cell and myeloid-derived suppressor cell populations. To confirm the effects of HSF on promotion of effector CD8[Formula: see text] T-cell production, we further evaluated changes in postoperative metastasis following treatment with HSF. Indeed, orthotopic lung metastasis was significantly suppressed, and survival times were increased in HSF-treated mice. Taken together, our findings suggested that HSF inhibited Lewis lung cancer by enhancing the population of effective CD8[Formula: see text] T cells.

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