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Seminars in Immunopathology Nov 2022CD4 and CD8 T lymphocytes mediate most of the adaptive immune response against tumors. Naïve T lymphocytes specific for tumor antigens are primed in lymph nodes by... (Review)
Review
CD4 and CD8 T lymphocytes mediate most of the adaptive immune response against tumors. Naïve T lymphocytes specific for tumor antigens are primed in lymph nodes by dendritic cells. Upon activation, antigen-specific T cells proliferate and differentiate into effector cells that migrate out of peripheral blood into tumor sites in an attempt to eliminate cancer cells. After accomplishing their function, most effector T cells die in the tissue, while a small fraction of antigen-specific T cells persist as long-lived memory cells, circulating between peripheral blood and lymphoid tissues, to generate enhanced immune responses when re-encountering the same antigen. A subset of memory T cells, called resident memory T (T) cells, stably resides in non-lymphoid peripheral tissues and may provide rapid immunity independently of T cells recruited from blood. Being adapted to the tissue microenvironment, T cells are potentially endowed with the best features to protect against the reemergence of cancer cells. However, when tumors give clinical manifestation, it means that tumor cells have evaded immune surveillance, including that of T cells. Here, we review the current knowledge as to how T cells are generated during an immune response and then maintained in non-lymphoid tissues. We then focus on what is known about the role of CD4 and CD8 T cells in antitumor immunity and their possible contribution to the efficacy of immunotherapy. Finally, we highlight some open questions in the field and discuss how new technologies may help in addressing them.
Topics: Humans; Lymphocyte Count; Lymphoid Tissue; Immunologic Surveillance; Immunotherapy; Memory T Cells
PubMed: 36385379
DOI: 10.1007/s00281-022-00970-4 -
Immunity Mar 2021
Topics: Allergy and Immunology; Antigen Presentation; Autoimmunity; History, 20th Century; History, 21st Century; Humans; Immunologic Surveillance; India; Male; Neoplasms; T-Lymphocytes; United States
PubMed: 33691123
DOI: 10.1016/j.immuni.2021.02.006 -
Trends in Immunology Apr 2017Cancers are often initiated by genetic events that activate proto-oncogenes or inactivate tumor-suppressor genes. These events are also crucial for sustained tumor cell... (Review)
Review
Cancers are often initiated by genetic events that activate proto-oncogenes or inactivate tumor-suppressor genes. These events are also crucial for sustained tumor cell proliferation and survival, a phenomenon described as oncogene addiction. In addition to this cell-intrinsic role, recent evidence indicates that oncogenes also directly regulate immune responses, leading to immunosuppression. Expression of many oncogenes or loss of tumor suppressors induces the expression of immune checkpoints that regulate the immune response, such as PD-L1. We discuss here how oncogenes, and in particular MYC, suppress immune surveillance, and how oncogene-targeted therapies may restore the immune response against tumors.
Topics: Animals; B7-H1 Antigen; Carcinogenesis; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Immune Tolerance; Immunologic Surveillance; Immunomodulation; Molecular Targeted Therapy; Neoplasms; Proto-Oncogene Proteins c-myc; Tumor Escape; Tumor Suppressor Proteins
PubMed: 28233639
DOI: 10.1016/j.it.2017.01.002 -
International Journal of Molecular... Jan 2020CD155 is an adhesion molecule belonging to the Nectin/Nectin-like family often overexpressed on tumor cells and involved in many different processes such as cell... (Review)
Review
CD155 is an adhesion molecule belonging to the Nectin/Nectin-like family often overexpressed on tumor cells and involved in many different processes such as cell adhesion, migration and proliferation. In contrast to these pro-tumorigenic functions, CD155 is also a ligand for the activating receptor DNAM-1 expressed on cytotoxic lymphocytes including Natural Killer (NK) cells and involved in anti-tumor immune response. However, during tumor progression inhibitory receptors for CD155 are up-regulated on the surface of effector cells, contributing to an impairment of their cytotoxic capacity. In this review we will focus on the roles of CD155 as a ligand for the activating receptor DNAM-1 regulating immune surveillance against cancer and as pro-oncogenic molecule favoring tumor proliferation, invasion and immune evasion. A deeper understanding of the multiple roles played by CD155 in cancer development contributes to improving anti-tumor strategies aimed to potentiate immune response against cancer.
Topics: Disease Progression; Humans; Immunologic Surveillance; Neoplasms; Receptors, Virus
PubMed: 32019260
DOI: 10.3390/ijms21030922 -
FEBS Letters Jun 2021Autophagy, the major lysosomal pathway for the degradation and recycling of cytoplasmic materials, is increasingly recognized as a major player in endothelial cell (EC)... (Review)
Review
Autophagy, the major lysosomal pathway for the degradation and recycling of cytoplasmic materials, is increasingly recognized as a major player in endothelial cell (EC) biology and vascular pathology. Particularly in solid tumors, tumor microenvironmental stress such as hypoxia, nutrient deprivation, inflammatory mediators, and metabolic aberrations stimulates autophagy in tumor-associated blood vessels. Increased autophagy in ECs may serve as a mechanism to alleviate stress and restrict exacerbated inflammatory responses. However, increased autophagy in tumor-associated ECs can re-model metabolic pathways and affect the trafficking and surface availability of key mediators and regulators of the interplay between EC and immune cells. In line with this, heightened EC autophagy is involved in pathological angiogenesis, inflammatory, and immune responses. Here, we review major cellular and molecular mechanisms regulated by autophagy in ECs under physiological conditions and discuss recent evidence implicating EC autophagy in tumor angiogenesis and immunosurveillance.
Topics: Animals; Autophagy; Autophagy-Related Proteins; Blood Vessels; Cytokines; Endothelial Cells; Gene Expression Regulation, Neoplastic; Homeostasis; Humans; Hypoxia; Immunologic Surveillance; Lysosomes; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Tumor Microenvironment
PubMed: 33837545
DOI: 10.1002/1873-3468.14087 -
Haematologica Mar 2017Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer. Multiple myeloma represents a genuine example of disrupted immune... (Review)
Review
Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer. Multiple myeloma represents a genuine example of disrupted immune surveillance characterized by: impaired antibody production, deregulation of the T and natural killer cell compartment, disruption of antigen presentation machinery, upregulation of inhibitory surface ligands, and recruitment of immunosuppressive cells. Although the potential value of immunotherapeutic interventions had a clear antecedent in the graft--myeloma effect induced by allogeneic stem cell transplant and donor lymphocyte infusions, it is only recently that this field has faced a real revolution. In this review we discuss the current results obtained with immune approaches in patients with multiple myeloma that have placed this disease under the scope of immuno-oncology, bringing new therapeutic opportunities for the treatment of multiple myeloma patients.
Topics: Animals; Antigens, Neoplasm; Cancer Vaccines; Combined Modality Therapy; Humans; Immune Evasion; Immunologic Surveillance; Immunotherapy; Molecular Targeted Therapy; Multiple Myeloma
PubMed: 28082344
DOI: 10.3324/haematol.2016.152504 -
Trends in Cell Biology Jan 2019Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical... (Review)
Review
Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy.
Topics: Humans; Immunologic Surveillance; Immunotherapy; Neoplasms; Wnt Proteins; Wnt Signaling Pathway
PubMed: 30220580
DOI: 10.1016/j.tcb.2018.08.005 -
Frontiers in Immunology 2018Tunneling nanotubes (TNT) are dynamic connections between cells, which represent a novel route for cell-to-cell communication. A growing body of evidence points TNT... (Review)
Review
Tunneling nanotubes (TNT) are dynamic connections between cells, which represent a novel route for cell-to-cell communication. A growing body of evidence points TNT towards a role for intercellular exchanges of signals, molecules, organelles, and pathogens, involving them in a diverse array of functions. TNT form among several cell types, including neuronal cells, epithelial cells, and almost all immune cells. In myeloid cells (e.g., macrophages, dendritic cells, and osteoclasts), intercellular communication TNT contributes to their differentiation and immune functions. Importantly, TNT enable myeloid cells to communicate with a targeted neighboring or distant cell, as well as with other cell types, therefore creating a complex variety of cellular exchanges. TNT also contribute to pathogen spread as they serve as "corridors" from a cell to another. Herein, we addressed the complexity of the definition and characterization of TNT in innate immune cells, the different processes involved in their formation, and their relevance . We also assess our current understanding of how TNT participate in immune surveillance and the spread of pathogens, with a particular interest for HIV-1. Overall, despite recent progress in this growing research field, we highlight that further investigation is needed to better unveil the role of TNT in both physiological and pathological conditions.
Topics: Animals; Cell Communication; HIV Infections; HIV-1; Humans; Immunity, Innate; Immunologic Surveillance; Mice; Myeloid Cells; Nanotubes; Rats
PubMed: 29422895
DOI: 10.3389/fimmu.2018.00043 -
Biochimica Et Biophysica Acta Mar 2016Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including... (Review)
Review
Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.
Topics: Antineoplastic Agents; Apoptosis; Cell Adhesion; Galectin 3; Humans; Immunologic Surveillance; Models, Immunological; Molecular Targeted Therapy; Neoplasms; Tumor Microenvironment
PubMed: 26264495
DOI: 10.1016/j.bbamcr.2015.08.008 -
Proceedings of the National Academy of... Oct 2023The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The...
The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor-immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell-immune cell contact in vivo in order to decipher the tumor-immune interactome. We call this approach, Tumor-Immune Interactome Non-biased Discovery Retroviral Reporter or TIINDRR. Using TIINDRR, we identify the tumor-immune interactomes that define immunological refractory and sensitive tumors and how different immunotherapies alter these interactions. Thus, TIINDRR provides a flexible and versatile tool for studying in-vivo tumor-immune cell interactions, aiding in the identification of biologically relevant information needed for the rational design of immune-based therapies.
Topics: Humans; Neoplasms; Cell Communication; Hydrolases; Immunologic Surveillance; Immunotherapy; Tumor Microenvironment
PubMed: 37871202
DOI: 10.1073/pnas.2306632120