scholarly journals Repurposing Infectious Pathogen Vaccines in Cancer Immunotherapy

2020 ◽  
Author(s):  
Matteo Conti
Keyword(s):  
Cancer Immunotherapy ◽  
Checkpoint Inhibitors ◽  
Mouse Tumor ◽  
Combined Approach ◽  
Anticancer Immunotherapy ◽  
Intratumoral Delivery ◽  
Infectious Pathogen ◽  
Novel Strategy ◽  
Mouse Tumor Models

Reports in the literature show that certain vaccines against infectious pathogens, can be effective in eliciting antitumor immune response when injected intratumorally. In mouse tumor models, intratumoral delivery of rotavirus, yellow fever, and influenza vaccines have been shown to also synergize with checkpoint inhibitors, in the leading immunotherapy in the clinical practice today. The combined approach can thus become a very promising novel strategy for anticancer immunotherapy. In humans, an attenuated poliomyelitis virus vaccine, a peptide-based vaccines against papilloma and one based on detoxified diphtheria protein have already been tested as intratumoral treatments readily. In those studies, the role of available anti-pathogen immunity appears an important element in mediating the activity of the repurposed vaccines against cancer. We therefore suggest how evaluating or eventually developing anti-pathogen immunity before intratumoral delivery could be helpful in repurposing infectious pathogen vaccines in cancer immunotherapy.

scholarly journals SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions

2016 ◽  
Vol 113 (5) ◽  
pp. E538-E547 ◽  
Author(s):  
Abhishek Bhardwaj ◽  
Sanjeev Das
Keyword(s):  
Tumor Suppressor ◽  
Nuclear Export ◽  
Genome Stability ◽  
Nuclear Protein ◽  
Glycolytic Enzyme ◽  
Mouse Tumor ◽  
Transcriptional Coactivator ◽  
Migration Potential ◽  
Mouse Tumor Models

SIRT6 (sirtuin 6) is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis, and tumorigenesis. However, the role of SIRT6 deacetylase activity in its tumor-suppressor functions is not well understood. Here we report that SIRT6 binds to and deacetylates nuclear PKM2 (pyruvate kinase M2) at the lysine 433 residue. PKM2 is a glycolytic enzyme with nonmetabolic nuclear oncogenic functions. SIRT6-mediated deacetylation results in PKM2 nuclear export. We further have identified exportin 4 as the specific transporter mediating PKM2 nuclear export. As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus, SIRT6 suppresses PKM2 oncogenic functions, resulting in reduced cell proliferation, migration potential, and invasiveness. Furthermore, studies in mouse tumor models demonstrate that PKM2 deacetylation is integral to SIRT6-mediated tumor suppression and inhibition of metastasis. Additionally, reduced SIRT6 levels correlate with elevated nuclear acetylated PKM2 levels in increasing grades of hepatocellular carcinoma. These findings provide key insights into the pivotal role of deacetylase activity in SIRT6 tumor-suppressor functions.

scholarly journals Establishment and application of a panel of PBMC-humanized mouse tumor models in cancer immunotherapy

2019 ◽  
Vol 30 ◽  
pp. i3
Author(s):  
L. Bourre ◽  
L. Zhang ◽  
S. Qi ◽  
H. Wu ◽  
L. Zhao ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Mouse Tumor ◽  
Humanized Mouse ◽  
Tumor Models ◽  
Mouse Tumor Models

Abstract 5677: Establishment and application of a panel of PBMC-humanized mouse tumor models in immune-oncology and targeted cancer immunotherapy

2018 ◽  
Author(s):  
Lan Zhang ◽  
Haochen Wu ◽  
Fei Chen ◽  
Lianqi Zhao ◽  
Xiaoyu An ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Mouse Tumor ◽  
Humanized Mouse ◽  
Tumor Models ◽  
Immune Oncology ◽  
Mouse Tumor Models

The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells

2019 ◽  
Vol 84 (7) ◽  
pp. 695-710 ◽  
Author(s):  
P. M. Gershovich ◽  
A. V. Karabelskii ◽  
A. B. Ulitin ◽  
R. A. Ivanov
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Checkpoint Inhibitors ◽  
Genetically Modified

Antitumor Activities of Immune Costimulatory Molecules of TNF Superfamily in Colorectal and Lung Cancers

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Liming Gui ◽  
◽  
Zhixue Wang ◽  
Pan Yin ◽  
Bin Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Costimulatory Molecules ◽  
Mouse Tumor ◽  
Antitumor Effects ◽  
Immune Effector ◽  
Lung Cancers ◽  
Tnf Superfamily

Cancer immunotherapy has emerged as a promising treatment that utilizes the innate or adaptive immunity to generate a robust killing of malignant cells. However, only a limited number of cancer patients showed responsiveness to immunotherapies such as checkpoint inhibitors, suggesting the need for potent alternative strategies. In the present study, we explored the therapeutic potentials of costimulatory molecules including TNF superfamily member 4 (TNFSF4), member 9 (TNFSF9), and member 18 (TNFSF18). In tumor samples from human colorectal and lung cancer patients, expression of these factors positively correlated with lymphocyte infiltration and expression of several immune effector genes. In syngeneic mouse tumor models, overexpression of the TNF superfamily costimulatory factors in murine colorectal or lung cancer cells significantly suppressed tumor progression. Especially, TNFSF9 and 18 showed stronger antitumor effects than TNFSF4. Together, our study demonstrated the great potential of cancer immunotherapy targeting these immune costimulatory molecules.

scholarly journals Fibroblastic reticular cells predict response to immune checkpoint inhibitors

2020 ◽  
Author(s):  
Daniele Biasci ◽  
James Thaventhiran ◽  
Simon Tavaré
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cancer Immunotherapy ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Reticular Cells

While the role of CD8+ T cells in mediating response to cancer immunotherapy is well established, the role of B cells remains more controversial (1–3). By conducting a large gene expression study of response to immune checkpoint inhibitors (ICI), we show that pre-treatment expression of B cell genes is associated with ICI response independently of CD8+ T cells. However, we discovered that such association can be completely explained by a single gene (FDCSP) expressed outside of the B cell compartment, in fibroblastic reticular cells (FRCs), which form the reticular network that facilitates interactions between B cells, T cells and cognate antigens (4–6) and are required to initiate efficient adaptive immune responses in secondary lymphoid organs (SLO) and tertiary lymphoid structures (TLS) (4, 7). We validated this finding in three independent cohorts of patients treated with ICI in melanoma and renal cell carcinoma. Taken together, these results suggest that FDCSP is an independent predictor of ICI response, thus opening new avenues to explain the mechanisms of resistance to cancer immunotherapy.

Resisting resistance: Homing in on better immunotherapy responses

2019 ◽  
Vol 11 (494) ◽  
pp. eaax9556
Author(s):  
Patrick M. Brunner
Keyword(s):  
Checkpoint Inhibitors ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Mouse Tumor Models

In mouse tumor models, the CXCR3-CXCL9 chemokine system mediates sensitivity to PD-1 blockade and could be exploited to enhance responsiveness to checkpoint inhibitors.

Abstract 4020: Inhibition of KITin vivomodifies immune cell populations to improve the efficacy of checkpoint inhibitors in syngeneic mouse tumor models

2016 ◽  
Author(s):  
Andrew J. Garton ◽  
Lori Lopresti-Morrow ◽  
Scott Seibel ◽  
Theresa LaVallee ◽  
Richard Gedrich
Keyword(s):  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cell Populations ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Syngeneic Mouse ◽  
Mouse Tumor Models
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