Chemokines and the immune response to cancer

Ozga, Aleksandra J.; Chow, Melvyn T.; Luster, Andrew D.

doi:10.1016/j.immuni.2021.01.012

Cited by 332 publications

(305 citation statements)

References 145 publications

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“…Nonetheless, decreased adhesion of SSMs may also suggest the need for increased mobility of those cellular processes tasked with phagocytosing lymph-borne material. The upregulation of CCL4 in SSMs by tumors is of particular interest as the cytokine has been involved in the recruitment of lymph node resident plasmacytoid and type-1 conventional dendritic cells (27). The former may explain how SSMs orchestrate type-I interferon responses (6,7,23).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer

et al. 2021

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Lymph nodes are key lymphoid organs collecting lymph fluid and migratory cells from the tissue area they survey. When cancerous cells arise within a tissue, the sentinel lymph node is the first immunological organ to mount an immune response. Sub-capsular sinus macrophages (SSMs) are specialized macrophages residing in the lymph nodes that play important roles as gatekeepers against particulate antigenic material. In the context of cancer, SSMs capture tumor-derived extracellular vesicles (tEVs), a form of particulate antigen released in high amounts by tumor cells. We and others have recently demonstrated that SSMs possess anti-tumor activity because in their absence tumors progress faster. A comprehensive profiling of SSMs represents an important first step to identify the cellular and molecular mechanisms responsible for SSM anti-tumor activity. Unfortunately, the isolation of SSMs for molecular analyses is very challenging. Here, we combined an optimized dissociation protocol, careful marker selection and stringent gating strategies to highly purify SSMs. We provide evidence of decreased T and B cell contamination, which allowed us to reveal the gene expression profile of this elusive macrophage subset. Squamous cell carcinomas induced an increase in the expression of Fc receptors, lysosomal and proteasomal enzymes in SSMs. Imaging of mouse and patient lymph nodes confirmed the presence of the top differentially expressed genes. These results suggest that SSMs respond to tumor formation by upregulating the machinery necessary for presentation of tumor particulate antigens to B cells.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer

et al. 2021

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“…The elimination of tumor cells relies heavily on the immune system in vivo and exogenous therapies, such as drugs or irradiation (96). The immune system is an intricate network that can guard the body by monitoring, recognizing, and eliminating foreign invaders, such as bacteria, parasites, and endogenous antigens like cancer cells (97). These days, when we talk about the relationship between immune response and tumors, programmed cell death protein 1 (PD-1) is one of the monumental works that are closely associated with it indeed (98).…”

Section: Immune Response and Therapy Resistancementioning

confidence: 99%

Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma

et al. 2021

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Esophageal squamous cell carcinoma (ESCC) persists among the most lethal and broad-spreading malignancies in China. The exosome is a kind of extracellular vesicle (EV) from about 30 to 200 nm in diameter, contributing to the transfer of specific functional molecules, such as metabolites, proteins, lipids, and nucleic acids. The paramount role of exosomes in the formation and development of ESCC, which relies on promoting intercellular communication in the tumor microenvironment (TME), is manifested with immense amounts. Tumor-derived exosomes (TDEs) participate in most hallmarks of ESCC, including tumorigenesis, invasion, angiogenesis, immunologic escape, metastasis, radioresistance, and chemoresistance. Published reports have delineated that exosome-encapsulated cargos like miRNAs may have utility in the diagnosis, as prognostic biomarkers, and in the treatment of ESCC. This review summarizes the function of exosomes in the neoplasia, progression, and metastasis of ESCC, which improves our understanding of the etiology and pathogenesis of ESCC, and presents a promising target for early diagnostics in ESCC. However, recent studies of exosomes in the treatment of ESCC are sparse. Thus, we introduce the advances in exosome-based methods and indicate the possible applications for ESCC therapy in the future.

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“…One reason why GBM is such an intractable tumor is because it can grow relatively unseen by the adaptive immune system until too late (i.e., when the tumor mass is large) [ 47 ]. This relative “invisibility” occurs at various steps of what should otherwise be the typical cancer immunity cycle: (1) release of tumor antigens, (2) antigen presentation by dendritic cells (DCs) and other professional antigen presenting cells (APCs), (3) priming and activation of T cells in secondary lymphoid tissues, (4) infiltration and engagement of the tumor by tumor-specific T cells [ 48 , 49 ]. Given that GBM is thought to be driven primarily by canonical mutations rather than carcinogens or other environmental perturbations, it harbors a far smaller neoantigen burden than other cancers [ 50 , 51 , 52 ].…”

Section: Endogenous Viruses Found In Gbmmentioning

confidence: 99%

Viral Control of Glioblastoma

Mihelson

McGavern

2021

Viruses

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Glioblastoma multiforme (GBM) is a universally lethal cancer of the central nervous system. Patients with GBM have a median survival of 14 months and a 5-year survival of less than 5%, a grim statistic that has remained unchanged over the last 50 years. GBM is intransigent for a variety of reasons. The immune system has a difficult time mounting a response against glioblastomas because they reside in the brain (an immunologically dampened compartment) and generate few neoantigens relative to other cancers. Glioblastomas inhabit the brain like sand in the grass and display a high degree of intra- and inter-tumoral heterogeneity, impeding efforts to therapeutically target a single pathway. Of all potential therapeutic strategies to date, virotherapy offers the greatest chance of counteracting each of the obstacles mounted by GBM. Virotherapy can xenogenize a tumor that is deft at behaving like “self”, triggering adaptive immune recognition in an otherwise immunologically quiet compartment. Viruses can also directly lyse tumor cells, creating damage and further stimulating secondary immune reactions that are detrimental to tumor growth. In this review, we summarize the basic immune mechanisms underpinning GBM immune evasion and the recent successes achieved using virotherapies.

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Chemokines and the immune response to cancer

Cited by 332 publications

References 145 publications

Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer

Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer

Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma

Viral Control of Glioblastoma

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