Abstract A98: Imprime PGG, a soluble yeast β glucan, primes innate immune effector cells to recognize and eradicate tumor cells

ABSTRACTRecent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: only adaptive immunity confers immunological memory and innate immunity lacks specificity. This work describes the novel observation that innate immune effector cells can be recruited to specific tissues of the body where pathology is present by using a microbial-based immune stimulus that consists of an inactivated pathogen that typically resides or causes infection in that target tissue site. We demonstrate this principle using experimental models of cancer and infection for which different subcutaneously delivered microbial-based treatments were shown to induce the recruitment of immune effector cells to specific diseased organs. Amelioration of disease in a given organ niche was dependent on matching the correct microbial stimulus for the affected organ site but was independent of the nature of the pathology. This observation intriguingly suggests that the immune system, upon pathogen recognition, tends to direct its resources to the compartment in which the pathogen has previously been encountered and would be the most likely source of infection. Importantly, this phenomenon provides a novel means to therapeutically target innate immune effector cells to sites of specific disease localization to potentially treat a wide spectrum of pathologies, including cancer, infection, and chronic inflammatory disorders.AUTHOR SUMMARYVaccines that target adaptive immune memory have revolutionized medicine. This study describes a novel strategy that works as a modified innate immune “vaccine” that exploits the trained response of innate immune effector cells to clear pathology in a specific tissue site. Unlike memory of the adaptive immune system, which functions like a lock and key, innate immune memory is more akin to a reflex response – like experienced muscle or neural cells that are changed by a stimulus to respond more efficiently upon re-exposure. This change in behavior through experience is the definition of learning. Our study suggests that this innate immune learning occurs at different levels. Emergency hematopoiesis trains new innate immune cells in the bone marrow to respond quickly and effectively to a non-specific threat; whereas, pathogen-specific training occurs at sites where cells making up the immunologic niche have had interactions with a particular pathogen and have been trained to respond more robustly to it upon re-presentation in the context of a danger signal. The speed with which new immune cells are trained in the bone marrow in response to an imminent microbial threat and their subsequent recruitment to the target organ site where that microbe typically resides suggests there are ways the immune system communicates to coordinate this rapid response that are yet to be fully delineated. These findings provide a novel highly proficient way to harness the potent effector functions of the innate immune system to address a wide range of immune-based diseases.

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Proteome characterization of sea star coelomocytes - The innate immune effector cells of echinoderms

PROTEOMICS ◽

10.1002/pmic.201000745 ◽

2011 ◽

Vol 11 (17) ◽

pp. 3587-3592 ◽

Cited By ~ 21

Author(s):

Catarina F. Franco ◽

Romana Santos ◽

Ana V. Coelho

Keyword(s):

Innate Immune ◽

Sea Star ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Innate Immune Effector

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Autoimmunity mediated by innate immune effector cells

Trends in Immunology ◽

10.1016/s1471-4906(01)01923-8 ◽

2001 ◽

Vol 22 (6) ◽

pp. 300-301 ◽

Cited By ~ 12

Author(s):

Jacques Zimmer ◽

Huguette Bausinger ◽

Henri de la Salle

Keyword(s):

Innate Immune ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Innate Immune Effector

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T Cell Memory to Vaccination

Vaccines ◽

10.3390/vaccines6040084 ◽

2018 ◽

Vol 6 (4) ◽

pp. 84 ◽

Cited By ~ 5

Author(s):

Stephen M Todryk

Keyword(s):

T Cells ◽

Immune Responses ◽

Cytotoxic T Lymphocytes ◽

Innate Immune ◽

T Cell Memory ◽

Immune Effector ◽

Effector Cells ◽

Vaccination Strategies ◽

Immune Effector Cells ◽

Innate Immune Effector

Most immune responses associated with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the generation, maintenance, activity, and measurement of such T cells is leading to vaccination strategies with greater efficacy and potentially greater microbial coverage.

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Fluorescent nanodiamonds engage innate immune effector cells: A potential vehicle for targeted anti-tumor immunotherapy

Nanomedicine Nanotechnology Biology and Medicine ◽

10.1016/j.nano.2016.12.005 ◽

2017 ◽

Vol 13 (3) ◽

pp. 909-920 ◽

Cited By ~ 13

Author(s):

Lorena P. Suarez-Kelly ◽

Amanda R. Campbell ◽

Isaac V. Rampersaud ◽

Ambika Bumb ◽

Min S. Wang ◽

...

Keyword(s):

Tumor Immunotherapy ◽

Innate Immune ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Innate Immune Effector ◽

Fluorescent Nanodiamonds

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Autoimmunity mediated by innate immune effector cells

Trends in Immunology ◽

10.1016/s1471-4906(01)01924-x ◽

2001 ◽

Vol 22 (6) ◽

pp. 301

Author(s):

Fu-Dong Shi ◽

Nora Sarvetnick ◽

Hans-Gustaf Ljunggren

Keyword(s):

Innate Immune ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Innate Immune Effector

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Mac-1 (CD11b/CD18) is crucial for effective Fc receptor–mediated immunity to melanoma

Blood ◽

10.1182/blood.v101.1.253 ◽

2003 ◽

Vol 101 (1) ◽

pp. 253-258 ◽

Cited By ~ 51

Author(s):

Annemiek B. van Spriel ◽

Heidi H. van Ojik ◽

Annie Bakker ◽

Marco J. H. Jansen ◽

Jan G. J. van de Winkel

Keyword(s):

Tumor Cells ◽

Lung Metastases ◽

Neutrophil Infiltration ◽

Fc Receptor ◽

Antibody Dependent Cellular Cytotoxicity ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Deficient Mice

Abstract Antibody-reliant destruction of tumor cells by immune effector cells is mediated by antibody-dependent cellular cytotoxicity, in which Fc receptor (FcR) engagement is crucial. This study documents an important role for the β2 integrin Mac-1 (CD11b/CD18) in FcR-mediated protection against melanoma. CD11b-deficient mice, those that lack Mac-1, were less protected by melanoma-specific monoclonal antibody TA99 than wild-type (WT) mice. Significantly more lung metastases and higher tumor loads were observed in Mac-1−/− mice. Histologic analyses revealed no differences in neutrophil infiltration of lung tumors between Mac-1−/− and WT mice. Importantly, Mac-1−/−phagocytes retained the capacity to bind tumor cells, implying that Mac-1 is essential during actual FcR-mediated cytotoxicity. In summary, this study documents Mac-1 to be required for FcR-mediated antimelanoma immunity in vivo and, furthermore, supports a role for neutrophils in melanoma rejection.

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Re-Expression of Poly/Oligo- Sialylated Adhesion Molecules on the Surface of Tumor Cells Disrupts Their Interaction with Immune-Effector Cells and Contributes to Pathophysiological Immune Escape

Cancers ◽

10.3390/cancers13205203 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5203

Author(s):

Mostafa Jarahian ◽

Faroogh Marofi ◽

Marwah Suliman Maashi ◽

Mahnaz Ghaebi ◽

Abdolrahman Khezri ◽

...

Keyword(s):

Cell Adhesion ◽

Tumor Cells ◽

Adhesion Molecules ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Immune Escape ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Cell Cell

Glycans linked to surface proteins are the most complex biological macromolecules that play an active role in various cellular mechanisms. This diversity is the basis of cell–cell interaction and communication, cell growth, cell migration, as well as co-stimulatory or inhibitory signaling. Our review describes the importance of neuraminic acid and its derivatives as recognition elements, which are located at the outermost positions of carbohydrate chains linked to specific glycoproteins or glycolipids. Tumor cells, especially from solid tumors, mask themselves by re-expression of hypersialylated neural cell adhesion molecule (NCAM), neuropilin-2 (NRP-2), or synaptic cell adhesion molecule 1 (SynCAM 1) in order to protect themselves against the cytotoxic attack of the also highly sialylated immune effector cells. More particularly, we focus on α-2,8-linked polysialic acid chains, which characterize carrier glycoproteins such as NCAM, NRP-2, or SynCam-1. This characteristic property correlates with an aggressive clinical phenotype and endows them with multiple roles in biological processes that underlie all steps of cancer progression, including regulation of cell–cell and/or cell–extracellular matrix interactions, as well as increased proliferation, migration, reduced apoptosis rate of tumor cells, angiogenesis, and metastasis. Specifically, re-expression of poly/oligo-sialylated adhesion molecules on the surface of tumor cells disrupts their interaction with immune-effector cells and contributes to pathophysiological immune escape. Further, sialylated glycoproteins induce immunoregulatory cytokines and growth factors through interactions with sialic acid-binding immunoglobulin-like lectins. We describe the processes, which modulate the interaction between sialylated carrier glycoproteins and their ligands, and illustrate that sialic acids could be targets of novel therapeutic strategies for treatment of cancer and immune diseases.

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