The development and functions of CD4+ T cells expressing a transgenic TCR specific for an MHC-I-restricted tumor antigenic epitope

Han, Xue; Ye, Peiying; Luo, Liqun; Zheng, Linghua; Liu, Yang; Chen, Lieping; Wang, Shengdian

doi:10.1038/cmi.2011.14

Cited by 3 publications

(4 citation statements)

References 18 publications

(19 reference statements)

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“…It has been reported that poly(I:C) as an adjuvant of tumor peptide vaccine induces memory CTL responses, in which CD4‐positive helper T cells play a supportive role . Regarding the effects on CD4 + T cells, our study took advantage of P1A‐sepcific TCR transgenic T cells, in which CD4 + T cells are capable of responding to P1A peptide in a MHC class I‐restricted manner, as reported by a previous study, and confirmed by our experiment (data not shown). Thus, we consider that the enhanced proliferation and cytokine productions of T cells by the combined adjuvant of poly(I:C) plus LAG‐3‐Ig might be mediated by CD4 + T cells to some extent; detailed functions of CD4 + T cells in our model need to be elucidated by further experiments.…”

Section: Discussionsupporting

confidence: 90%

“…In contrast, almost no changes in BTLA expression levels were observed by the combined adjuvant of poly(I:C) plus LAG‐3‐Ig, compared to IFA. As it was reported that CD4‐positive, Vα8.3‐positive T cells from P1A‐TCR transgenic mice also recognize P1A epitope and exert cytotoxic functions against P815 tumor, we further examined exhaustion markers on CD4/Vα8.3 double‐positive T cells. Similarly to P1A‐specific CTL, expressions of PD‐1, LAG‐3, and TIGIT, but not BTLA, on CD4‐positive P1A‐specific T cells were downregulated by the combined adjuvant poly(I:C) plus LAG‐3‐Ig (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Combined adjuvants of poly(I:C) plus LAG‐3‐Ig improve antitumor effects of tumor‐specific T cells, preventing their exhaustion

et al. 2016

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Therapeutic cancer vaccines are designed to treat cancer by boosting the endogenous immune system to fight against the cancer. In the development of clinically effective cancer vaccines, one of the most practical objectives is to identify adjuvants that are capable of optimizing the vaccine effects. In this study, we explored the potential of polyinosinic–polycytidylic acid (poly(I:C)) and LAG‐3‐Ig (soluble recombinant protein of lymphocyte activation gene‐3 [LAG‐3] extracellular domain fused with human IgG Fc region) as adjuvants for P1A tumor antigen peptide vaccine in a pre‐established P815 mouse tumor model with a transfer of tumor‐specific T cells. Whereas the use of poly(I:C) or LAG‐3‐Ig as a signal adjuvant induced a slight enhancement of P1A vaccine effects compared to incomplete Freund's adjuvant, combined treatment with poly(I:C) plus LAG‐3‐Ig remarkably potentiated antitumor effects, leading to complete rejection of pre‐established tumor and long‐term survival of mice. The potent adjuvant effects of poly(I:C) plus LAG‐3‐Ig were associated with an enhanced infiltration of T cells in the tumor tissues, and an increased proliferation and Th1‐type cytokine production of tumor‐reactive T cells. Importantly, the combined adjuvant of poly(I:C) plus LAG‐3‐Ig downregulated expressions of PD‐1, LAG‐3, and TIGIT on P1A‐specific T cells, indicating prevention of T cell exhaustion. Taken together, the results of the current study show that the combined adjuvants of poly(I:C) plus LAG‐3‐Ig with tumor peptide vaccine induce profound antitumor effects by activating tumor‐specific T cells.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Combined adjuvants of poly(I:C) plus LAG‐3‐Ig improve antitumor effects of tumor‐specific T cells, preventing their exhaustion

et al. 2016

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“…The stained cells were washed and analyzed by flow cytometry LSR II (BD Canto II, New Jersey, USA). Details of flow cytometry analysis can be found in our previous report 38 .…”

Section: Methodsmentioning

confidence: 99%

YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment

Yang

Lam

Jiang

et al. 2021

Sci Rep

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YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.

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“…The stained cells were washed and analyzed by ow cytometry LSR II (BD Canto II, New Jersey, USA). Details of ow cytometry analysis can be found in our previous report 38 .…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

YIV-906 Potentiated anti-PD1 Action Against Hepatocellular Carcinoma by Enhancing Adaptive and Innate Immunity in the Tumor Microenvironment.

Yang

Lam

Jiang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach - inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PDL1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of IFNg to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.

show abstract

The development and functions of CD4+ T cells expressing a transgenic TCR specific for an MHC-I-restricted tumor antigenic epitope

Cited by 3 publications

References 18 publications

Combined adjuvants of poly(I:C) plus LAG‐3‐Ig improve antitumor effects of tumor‐specific T cells, preventing their exhaustion

Combined adjuvants of poly(I:C) plus LAG‐3‐Ig improve antitumor effects of tumor‐specific T cells, preventing their exhaustion

YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment

YIV-906 Potentiated anti-PD1 Action Against Hepatocellular Carcinoma by Enhancing Adaptive and Innate Immunity in the Tumor Microenvironment.

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