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

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.

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.

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 microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

2020 ◽  
Vol 21 (8) ◽  
pp. 2805 ◽  
Author(s):  
Marta Gomarasca ◽  
Paola Maroni ◽  
Giuseppe Banfi ◽  
Giovanni Lombardi
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Formation Process ◽  
Immune Escape ◽  
Antitumor Immune Response ◽  
Metastasis Formation ◽  
Biological Mechanisms ◽  
Aberrant Expression

Breast cancer is the most common type of cancer in women, and the occurrence of metastasis drastically worsens the prognosis and reduces overall survival. Understanding the biological mechanisms that regulate the transformation of malignant cells, the consequent metastatic transformation, and the immune surveillance in the tumor progression would contribute to the development of more effective and targeted treatments. In this context, microRNAs (miRNAs) have proven to be key regulators of the tumor-immune cells crosstalk for the hijack of the immunosurveillance to promote tumor cells immune escape and cancer progression, as well as modulators of the metastasis formation process, ranging from the preparation of the metastatic site to the transformation into the migrating phenotype of tumor cells. In particular, their deregulated expression has been linked to the aberrant expression of oncogenes and tumor suppressor genes to promote tumorigenesis. This review aims at summarizing the role and functions of miRNAs involved in antitumor immune response and in the metastasis formation process in breast cancer. Additionally, miRNAs are promising targets for gene therapy as their modulation has the potential to support or inhibit specific mechanisms to negatively affect tumorigenesis. With this perspective, the most recent strategies developed for miRNA-based therapeutics are illustrated.

scholarly journals Strategies for Enhancing Vaccine-Induced CTL Antitumor Immune Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xin Yong ◽  
Yü-Feng Xiao ◽  
Gang Luo ◽  
Bin He ◽  
Mu-Han Lü ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Tumor Antigens ◽  
Critical Role ◽  
Antitumor Immune Response ◽  
Tumor Vaccines ◽  
Cytotoxic Effects

Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendritic cells (DCs) must capture antigens derived from exogenous tumor vaccines in vivo or autologous DCs directly loaded in vitro with tumor antigens must be injected. Next, tumor-antigen-loaded DCs must activate CTLs in lymphoid organs. Subsequently, activated CTLs must enter the tumor microenvironment to perform their functions, at which point a variety of negative regulatory signals suppress the immune response. Finally, CTL-mediated cytotoxic effects must overcome the tolerance induced by tumor cells. Each step is a complex process that may be impeded in many ways. However, if these steps happen under appropriate regulation, the vaccine-induced CTL antitumor immune response will be more successful. For this reason, we should gain a better understanding of the basic mechanisms that govern the immune response. This paper, based on the steps necessary to induce an immune response, discusses current strategies for enhancing vaccine-induced CTL antitumor immune responses.

scholarly journals Expression of Fas (CD95/APO-1) Ligand by Human Breast Cancers: Significance for Tumor Immune Privilege

1999 ◽  
Vol 6 (4) ◽  
pp. 457-463 ◽  
Author(s):  
Joe O’Connell ◽  
Michael W. Bennett ◽  
Gerald C. O’Sullivan ◽  
Jim O’Callaghan ◽  
J. Kevin Collins ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Breast Tumors ◽  
Immune Privilege ◽  
Antitumor Immune Response ◽  
Cell Surface Receptor ◽  
Tumor Type ◽  
Breast Cancers ◽  
Activated Lymphocytes

ABSTRACT Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.

scholarly journals Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yamin Yang ◽  
Yue Hu ◽  
Hongjun Wang
Keyword(s):  
Immune Response ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Model Development ◽  
Antitumor Immune Response ◽  
Future Perspectives ◽  
Adaptive Immune ◽  
Photodynamic Therapy Of Cancer ◽  
Direct Cytotoxicity

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response.

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