Abstract LB-228: Imprime PGG treatment elicits a coordinated antitumor immune response that triggers enhanced expression of PD-L1 on tumor cells as well as monocyte-derived macrophages and dendritic cells

2015 ◽  
Author(s):  
Nandita Bose ◽  
Anissa SH Chan ◽  
Adria Jonas ◽  
Xiaohong Qiu ◽  
Nadine R. Ottoson ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Cells ◽  
Antitumor Immune Response ◽  
Enhanced Expression

scholarly journals Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3386
Author(s):  
Bart Spiesschaert ◽  
Katharina Angerer ◽  
John Park ◽  
Guido Wollmann
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Small Molecule ◽  
Antiviral Immunity ◽  
Oncolytic Viruses ◽  
Antitumor Immune Response ◽  
Antiviral Responses ◽  
Small Molecule Therapeutics ◽  
Immunosuppressive Factors

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

A new strategy for enhancing antitumor immune response using dendritic cells loaded with chemo-resistant cancer stem-like cells in experimental mice model

2019 ◽  
Vol 111 ◽  
pp. 106-117 ◽  
Author(s):  
Nahla E. El-Ashmawy ◽  
Enas A. El-Zamarany ◽  
Mohamed L. Salem ◽  
Eman G. Khedr ◽  
Amera O. Ibrahim
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Antitumor Immune Response ◽  
Mice Model ◽  
New Strategy

scholarly journals Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
François Ghiringhelli ◽  
Mélanie Bruchard ◽  
Fanny Chalmin ◽  
Cédric Rébé
Keyword(s):  
Immune Response ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
T Cell Response ◽  
Antitumor Immune Response ◽  
Tumor Bed ◽  
Wide Range ◽  
Key Factor ◽  
The Impact

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response.

scholarly journals Control of the Antitumor Immune Response by Cancer Metabolism

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 104 ◽  
Author(s):  
Charlotte Domblides ◽  
Lydia Lartigue ◽  
Benjamin Faustin
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Cancer Metabolism ◽  
Hematological Malignancies ◽  
Immune Cell ◽  
Immune Escape ◽  
Positive Impact ◽  
Metabolic Reprogramming ◽  
Antitumor Immune Response ◽  
Molecular Events

The metabolic reprogramming of tumor cells and immune escape are two major hallmarks of cancer cells. The metabolic changes that occur during tumorigenesis, enabling survival and proliferation, are described for both solid and hematological malignancies. Concurrently, tumor cells have deployed mechanisms to escape immune cell recognition and destruction. Additionally, therapeutic blocking of tumor-mediated immunosuppression has proven to have an unprecedented positive impact in clinical oncology. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune signaling through both the release of signaling molecules and the expression of immune membrane ligands. Here, we review these molecular events to highlight the contribution of cancer cell metabolic reprogramming on the shaping of the antitumor immune response.

scholarly journals Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Li ◽  
Mingyou Zhang ◽  
Xiaodan Wang ◽  
Wentao Liu ◽  
Hui Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Antitumor Immune Response

Role of the inflammasome of tumor cells in modulating the biology of Tumor Infiltrating T lymphocytes (TILs) in colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23087-e23087
Author(s):  
Anne Jarry ◽  
Adrien Ouairy ◽  
Delphine Dansette ◽  
Cécile Deleine ◽  
Nicolas Jouand ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Retrospective Cohort ◽  
Ex Vivo ◽  
High Density ◽  
Antitumor Immune Response ◽  
Caspase 1 ◽  
Active Caspase

e23087 Background: In colorectal cancer (CRC), little is known about mechanisms by which tumor cells can influence the phenotype and biology of Tumor Infiltrating T lymphocytes (TILs) of the tumor microenvironment. One of these mechanisms could be the inflammasome, a molecular platform present in normal intestinal epithelial cells, whose effector protein, caspase-1, can rapidly mature IL18 and generate a mucosal Th1/Tc1 (IFNγ) response. However, the inflammasome status of tumor cells in CRC and its potential role on TILs are unknown yet. Methods: Prospective and retrospective cohort studies aimed to determine in CRC patients: the status of the inflammasome in tumor cells (IL18 immunostaining on tissue microarrays (TMA) and in situ detection of active caspase-1 on frozen sections) and the density of TILs (CD8+, T-bet+) in relation with i) the microsatellite stable (MSS) or unstable (MSI) status of CRC, and ii) the levels of cytokines (IL18, IFNγ) secreted in an ex vivo explant culture model of CRC. Finally, we assessed the effect of recombinant human IL18 (rhIL18) on the IFNγ response of isolated TILs. Results: TMA analysis of the retrospective cohort showed that IL18 was significantly expressed (in more than 50% of tumor cells) in 80% of CRC, especially in MSI CRC, and correlated with a high density of T-bet+ and CD8+ intraepithelial TILs (IEL-TILs). Active caspase-1 was detected in tumor cells in 60% of CRC. In the prospective cohort, the presence of active caspase-1 in tumor cells was associated with high levels of mature IL18 secreted in explant cultures, with high density of T-bet+ TILs and with IFNγ release in most cases. In addition, isolated TILs expressing IL18 receptors (IL18Rα), cultured with rhIL18, were able to secrete IFNγ either unstimulated or stimulated with OKT3. Conclusions: The inflammasome of tumor cells, when maintained and active, can contribute to a Th1/Tc1 antitumor immune response elicited by TILs, that can modulate tumor growth. The inflammasome of tumor cells can thus be considered as a potential new therapeutic target to strengthen the antitumor immune response in CRC, in association with other immunotherapies.

Role of the inflammasome of tumor cells in modulating the biology of Tumor Infiltrating T lymphocytes (TILs) in colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 640-640
Author(s):  
Celine Bossard ◽  
Delphine Dansette ◽  
Adrien Ouairy ◽  
Nicolas Jouand ◽  
Romain Oger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Retrospective Cohort ◽  
Ex Vivo ◽  
High Density ◽  
Antitumor Immune Response ◽  
Caspase 1 ◽  
Active Caspase

640 Background: In colorectal cancer (CRC), little is known about mechanisms by which tumor cells can influence the phenotype and biology of Tumor Infiltrating T lymphocytes (TILs) of the tumor microenvironment. One of these mechanisms could be the inflammasome, a molecular platform present in normal intestinal epithelial cells, whose effector protein, caspase-1, can rapidly mature IL18 and generate a mucosal Th1/Tc1 (IFNg) response. However, the inflammasome status of tumor cells in CRC and its potential role on TILs are unknown yet. Methods: Prospective and retrospective cohort studies aimed to determine in CRC patients: the status of the inflammasome in tumor cells (IL18 immunostaining on tissue microarrays (TMA) and in situ detection of active caspase-1 on frozen sections) and the density of TILs (CD8+, T-bet+) in relation with the microsatellite stable (MSS) or unstable (MSI) status of CRC, and the levels of cytokines (IL18, IFNg) secreted in an ex vivo explant culture model of CRC. Finally, we assessed the effect of recombinant human IL18 (rhIL18) on the IFNg response of isolated TILs. Results: TMA analysis of the retrospective cohort showed that IL18 was significantly expressed (in more than 50% of tumor cells) in 80% of CRC, especially in MSI CRC, and correlated with a high density of T-bet+ and CD8+ intraepithelial TILs (IEL-TILs). Active caspase-1 was detected in tumor cells in 60% of CRC. In the prospective cohort, the presence of active caspase-1 in tumor cells was associated with high levels of mature IL18 secreted in explant cultures, with high density of T-bet+ TILs and with IFNg release in most cases. In addition, isolated TILs expressing IL18 receptors (IL18Ra), cultured with rhIL18, were able to secrete IFNg either unstimulated or stimulated with OKT3. Conclusions: The inflammasome of tumor cells, when maintained and active, can contribute to a Th1/Tc1 antitumor immune response elicited by TILs, that can modulate tumor growth. The inflammasome of tumor cells can thus be considered as a potential new therapeutic target to strengthen the antitumor immune response in CRC, in association with other immunotherapies.

scholarly journals Inhibition of Phosphatidylserine Recognition Heightens the Immunogenicity of Irradiated Lymphoma Cells In Vivo

2004 ◽  
Vol 200 (9) ◽  
pp. 1157-1165 ◽  
Author(s):  
Attilio Bondanza ◽  
Valérie S. Zimmermann ◽  
Patrizia Rovere-Querini ◽  
Javier Turnay ◽  
Ingrid E. Dumitriu ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Cells ◽  
Proinflammatory Cytokines ◽  
Annexin V ◽  
Immune Rejection ◽  
Lymphoma Cells ◽  
High Affinity ◽  
Tumor Specific Immune Response

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages. Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor. The response was endowed with both memory, because protected animals rejected living lymphoma cells after 72 d, and specificity, because vaccinated animals failed to reject unrelated neoplasms. Finally, AxV–coupled irradiated cells induced the regression of growing tumors. These data indicate that endogenous adjuvants that bind to dying tumor cells can be exploited to target tumors for immune rejection.

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