Calreticulin acts as an adjuvant to promote dendritic cell maturation and enhances antigen-specific cytotoxic T lymphocyte responses against non-small cell lung cancer cells

Liu, Xinli; Li, Jijia; Lu, Yu; Ding, Jianqiao; Tong, Zhuang; Liu, Yang; Zhou, Yang; Liu, Yongyu

doi:10.1016/j.cellimm.2015.12.003

Cited by 34 publications

(21 citation statements)

References 33 publications

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“…Recent research has demonstrated the important role of CALR in anti-tumor activity by increasing dendritic cell maturation, tumor antigen presentation and priming of CD8+ cells (30,45). CALR expression level is considered as an important indicator of tumor prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

et al. 2020

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Section: Discussionmentioning

confidence: 99%

“…Thus, the CALR-activated dendritic cells have potent activity in priming anti-tumor cytotoxic CD8+ T lymphocytes (CTLs) and CALR is a potential molecular target in anti-tumor immunotherapy (30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

et al. 2020

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“…O'Beirne et al assessed the function of GPC-3 specific T cells in HCC 11 . Moreover, DC-CTLs therapy additionally held promise for the treatment of other malignant tumors, including non-small cell lung cancer (NSCLC) 12 and prostate cancer 13 .…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells

Wang¹,

Yang²,

Yu³

et al. 2018

J. Cancer

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Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC).Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method.Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8. Levels of IFN-γ and TNF-α were higher in the DCs pulsed with tumor-associated antigens (TAAs) than in DCs with a non-proliferative recombinant adenovirus. The percentage of regulatory T cells (Tregs) decreased in patients after DC-CTLs therapy. In addition, serum levels of AFP, AFP-L3, ALT, and CA19-9 were significantly reduced in these patients. Quality of life was improved, especially on physical functioning scales. Median overall survival (OS) and progression-free survival (PFS) were 8.2 months and 4.3 months, respectively, for the control group and 12.8 months and 9 months, respectively, for the DC-CTL group. Patients treated with DC-CTLs therapy showed a statistically significant PFS and OS curve (OS: p=0.016; PFS: p<0.0001). In addition, no serious adverse reactions were observed.Conclusion This study indicated that Tregs, as well as serum levels of AFP, AFP-L3, ALT, and CA19-9, which were correlated with a poor prognosis, decreased after DC-CTL treatments. The OS, PFS and the quality of life of HCC patients partially improved.

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“…Through interaction with the DC ligands on cell surface, phagocytosis and tumor antigen presentation of DC are enhanced. This results in the formation of specifically sensitized lymphocytes with reconstructed immune pattern within tumor [ 32 ]. When CRT was knockout, immune responses such as the activation of DC by apoptotic cells also disappeared [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress-mediated membrane expression of CRT/ERp57 induces immunogenic apoptosis in drug-resistant endometrial cancer cells

Chen

et al. 2017

Oncotarget

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ObjectiveTo investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro.MethodsThe expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer. The protein expression of PERK, cleaved-caspase-8, p-eIF2α and CHOP were detected by Western blot, and the expression of VAMP-1, SNAP23 and PERK was knockdown by siRNA and/or shRNA. The expression of CRT/ERp57 complex was detected by flow cytometry. In addition, the expression of eIF2α and p-eIF2α was detected by Western blot analysis after drug-resistant EC cells were transfected with lentivirus overexpressing CRT, treated with GADD34 inhibitor and ES stress inducer. MTT assay was used to detect the phagocytic activity of T cells induced by maturation of dendritic cells in drug-resistant EC cells.ResultsThe expression of CRT, ERp57, p-PERK and p-eIF2α was significantly decreased in the drug-resistant patients in EC patients. The IC50 of the drug-resistant EC cells was 10 times higher than that of the wild type cells. In the drug-resistant EC cells the expression of CRT, ERp57, p-PERK, p-eIF2α, caspase-8 and CHOP was significantly lower than in the wild type cells. After treatment with DOX, CRT and ER stress-related proteins p-PERK, p-eIF2α, caspase-8 and apoptosis were significantly increased in wild-type EC cells, but not in drug-resistant EC cells. The increased expressions led to inhibition of cell growth and apoptosis. The knockdown of PERK gene and addition of DOX resulted in significant decrease of cleaved-caspase 8 and p-eIF2α in sensitive EC cells. The expression of CRT/ERp57 in sensitive EC cells was further significantly decreased by blocking VAMP and SNAP23. In addition, transfection with CRT overexpressing lentivirus and addition of GADD34 inhibitor and ER stress inducer in drug-resistant EC cells revealed a significant increase in the expression of CRT/ERp57 complex and p-eIF2α when DOX was added simultaneously, which promoted the maturation and chemotaxis of T lymphocytes to phagocytose drug-resistant EC cells.ConclusionDOX can induce the death of tumor cells by ER stress-mediated CRT/ERp57 expression in EC cells. Induction of ER stress in drug-resistant EC cells up-regulates the membrane expression of CRT/ERp57, enhances phagocytosis, induces immunogenic apoptosisand sensitizes the cells to DOX.

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Calreticulin acts as an adjuvant to promote dendritic cell maturation and enhances antigen-specific cytotoxic T lymphocyte responses against non-small cell lung cancer cells

Cited by 34 publications

References 33 publications

Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

Calreticulin Blockade Attenuates Murine Acute Lung Injury by Inducing Polarization of M2 Subtype Macrophages

Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells

Endoplasmic reticulum stress-mediated membrane expression of CRT/ERp57 induces immunogenic apoptosis in drug-resistant endometrial cancer cells

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