Immune Checkpoint Molecules and Cancer Immunotherapy

2019 ◽  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Molecules

scholarly journals Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yuqing Cao ◽  
Xiaoyu Wang ◽  
Tianqiang Jin ◽  
Yu Tian ◽  
Chaoliu Dai ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Natural Killer ◽  
Immune Checkpoint ◽  
Therapeutic Target ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Immune Checkpoints ◽  
Immune Checkpoint Molecules

Abstract Recent studies have demonstrated the potential of natural killer (NK) cells in immunotherapy to treat multiple types of cancer. NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex. The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers. NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy. The effector role of these cells is reliant on the balance of inhibitory and activating signals. Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation. Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment; this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers. Accordingly, this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function, as well as their potential application in tumor immunotherapy.

scholarly journals Editorial: Immune Checkpoint Molecules and Cancer Immunotherapy

2018 ◽  
Vol 9 ◽  
Author(s):  
Alexandr V. Bazhin ◽  
Amedeo Amedei ◽  
Svetlana Karakhanova
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Molecules

scholarly journals Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy

2017 ◽  
Vol 108 (4) ◽  
pp. 574-580 ◽  
Author(s):  
Shunsuke Chikuma ◽  
Mitsuhiro Kanamori ◽  
Setsuko Mise-Omata ◽  
Akihiko Yoshimura
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Cytokine Signaling ◽  
Immune Checkpoint Molecules ◽  
Suppressors Of Cytokine Signaling

scholarly journals Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Host Immune Responses ◽  
Near Future ◽  
Identification And Characterization

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.

scholarly journals Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoqing Luo ◽  
Shunli Peng ◽  
Sijie Ding ◽  
Qin Zeng ◽  
Rong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Tissue Array ◽  
Lung Cancers ◽  
Cox Regression Analysis ◽  
Immune Checkpoint Molecules ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Infiltration Models

Abstract Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

scholarly journals Combined Inhibition of TGF-β1-Induced EMT and PD-L1 Silencing Re-Sensitizes Hepatocellular Carcinoma to Sorafenib Treatment

2021 ◽  
Vol 10 (9) ◽  
pp. 1889
Author(s):  
Ritu Shrestha ◽  
Prashanth Prithviraj ◽  
Kim R. Bridle ◽  
Darrell H. G. Crawford ◽  
Aparna Jayachandran
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Treatment ◽  
Immune Checkpoint ◽  
Post Treatment ◽  
Immune Checkpoints ◽  
Sorafenib Treatment ◽  
Mesenchymal Transition ◽  
Immune Checkpoint Molecules ◽  
Tgf Β1 ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is the most common type of primary hepatic malignancy. HCC is one of the leading causes of cancer deaths worldwide. The oral multi-tyrosine kinase inhibitor Sorafenib is the standard first-line therapy in patients with advanced unresectable HCC. Despite the significant survival benefit in HCC patients post treatment with Sorafenib, many patients had progressive disease as a result of acquiring drug resistance. Circumventing resistance to Sorafenib by exploring and targeting possible molecular mechanisms and pathways is an area of active investigation worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process allowing epithelial cells to assume mesenchymal traits. HCC tumour cells undergo EMT to become immune evasive and develop resistance to Sorafenib treatment. Immune checkpoint molecules control immune escape in many tumours, including HCC. The aim of this study is to investigate whether combined inhibition of EMT and immune checkpoints can re-sensitise HCC to Sorafenib treatment. Post treatment with Sorafenib, HCC cells PLC/PRF/5 and Hep3B were monitored for induction of EMT and immune checkpoint molecules using quantitative reverse transcriptase (qRT)- PCR, western blot, immunofluorescence, and motility assays. The effect of combination treatment with SB431542, a specific inhibitor of the transforming growth factor (TGF)-β receptor kinase, and siRNA mediated knockdown of programmed cell death protein ligand-1 (PD-L1) on Sorafenib resistance was examined using a cell viability assay. We found that three days of Sorafenib treatment activated EMT with overexpression of TGF-β1 in both HCC cell lines. Following Sorafenib exposure, increase in the expression of PD-L1 and other immune checkpoints was observed. SB431542 blocked the TGF-β1-mediated EMT in HCC cells and also repressed PD-L1 expression. Likewise, knockdown of PD-L1 inhibited EMT. Moreover, the sensitivity of HCC cells to Sorafenib was enhanced by combining a blockade of EMT with SB431542 and knockdown of PD-L1 expression. Sorafenib-induced motility was attenuated with the combined treatment of SB431542 and PD-L1 knockdown. Our findings indicate that treatment with Sorafenib induces EMT and expression of immune checkpoint molecules, which contributes to Sorafenib resistance in HCC cells. Thus, the combination treatment strategy of inhibiting EMT and immune checkpoint molecules can re-sensitise HCC cells to Sorafenib.

scholarly journals Eight-Color Multiplex Immunohistochemistry for Simultaneous Detection of Multiple Immune Checkpoint Molecules within the Tumor Microenvironment

2017 ◽  
Vol 200 (1) ◽  
pp. 347-354 ◽  
Author(s):  
Mark A. J. Gorris ◽  
Altuna Halilovic ◽  
Katrin Rabold ◽  
Anne van Duffelen ◽  
Iresha N. Wickramasinghe ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Simultaneous Detection ◽  
Immune Checkpoint Molecules

scholarly journals 836 Releasing the restraints of Vγ9Vδ2 T-cells in cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A888-A888
Author(s):  
Laura Ridgley ◽  
Angus Dalgleish ◽  
Mark Bodman-Smith
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Tumour Cell ◽  
Immune Checkpoint ◽  
Expansion Method ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Inhibitory Receptors ◽  
Healthy Donors ◽  
Vγ9vδ2 T Cells

BackgroundVγ9Vδ2 T-cells are a subset of cells with a crucial role in immunosurveillance which can be activated and expanded by multiple means to stimulate effector responses, often exploited in cancer immunotherapy. Little is known about the expression of checkpoint molecules on this cell population and whether the ligation of these molecules can regulate their activity. The aim of this study was to assess the expression of activatory and inhibitory markers on Vγ9Vδ2 T-cells to assess potential avenues of regulation to target with immunotherapy.MethodsPBMCs were isolated from healthy donors and the expression of activatory and inhibitory receptors was assessed on Vγ9Vδ2 T-cells by flow cytometry at baseline, following 24 hours activation and 14 days expansion using zoledronic acid (ZA) and Bacillus Calmette-Guerin (BCG), both with IL-2. Activation and expansion of Vδ2 cells was assessed by expression of CD69 and by frequency of Vδ2 cells, respectively. Production of effector molecules was also assessed following coculture with various tumour cell targets. The effect of immune checkpoint blockade on Vγ9Vδ2 T-cells was also assessed.ResultsVγ9Vδ2 T-cells constitutively expressed high levels of NK-associated activatory markers NKG2D and DNAM1 which remained high following stimulation with ZA and BCG. Vγ9Vδ2 T-cells expressed variable levels of checkpoint inhibitor molecules at baseline with high levels of BTLA, KLRG1 and NKG2A and intermediate levels of PD1, TIGIT and VISTA. Expression of checkpoint receptors were modulated following activation and expansion with ZA and BCG with decreased expression of BTLA and upregulation of numerous markers including PD1, TIGIT, TIM3, LAG3 and VISTA. Expression of these markers is further modulated upon coculture with tumour cell lines with changes reflecting activation of these cells with Vγ9Vδ2 T-cells expressing inhibitory receptors PD1 and NKG2A producing the highest level of TNF.ConclusionsOur data reveals unique characteristics of Vδ2 in terms of their expression of immune checkpoints, which provide a mechanism which may be utilised by tumour cells to subvert Vγ9Vδ2 T-cell cytotoxicity. Our work suggests different profiles of immune checkpoints dependent on the method of stimulation. This highlights importance of expansion method in the function of Vγ9Vδ2 T-cells. Furthermore, this work suggests important candidates for blockade by immune checkpoint therapy in order to increase the successful use of Vγ9Vδ2 T-cells in cancer immunotherapy.

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