The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy

It has long been understood that the control and surveillance of tumors within the body involves an intricate dance between the adaptive and innate immune systems. At the center of the interplay between the adaptive and innate immune response sits the complement system- an evolutionarily ancient response that aids in the destruction of microorganisms and damaged cells, including cancer cells. Membrane-bound complement regulatory proteins, (mCRPs) such as CD46, CD55 and CD59, are expressed throughout the body in order to prevent over-activation of the complement system. These mCRPs act as a double-edged sword however, as they can also over-regulate the complement system to the extent that it is no longer effective at eliminating cancerous cells. Recent studies are now indicating that mCRPs may function as a biomarker of a malignant transformation in numerous cancer types, and further, are being shown to interfere with anti-tumor treatments. This highlights the critical roles that therapeutic blockade of mCRPs can play in cancer treatment. Furthermore, with the complement system having the ability to both directly and indirectly control adaptive T-cell responses, the use of a combinatorial approach of complement-related therapy along with other T-cell activating therapies becomes a logical approach to treatment. This review will highlight the biomarker related role that mCRP expression may have in the classification of tumor phenotype and predicted response to different anti-ca...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

Go online to PeerView.com/DHV860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Immune checkpoint inhibitor therapy is the new standard of care for patients with stage III, unresectable NSCLC who have not had disease progression after concurrent chemoradiotherapy. Immunotherapy-based treatment approaches are also being explored in multiple clinical trials in neoadjuvant and adjuvant settings in earlier stages of lung cancer. What is the rationale for and the evidence supporting the use of immunotherapy in locally advanced and early-stage lung cancer? How can we optimally...
Source: PeerView CME/CE Audio Podcast - Oncology - Category: Cancer & Oncology Authors: Tags: Science, Medicine Source Type: podcasts
Go online to PeerView.com/FJP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Cancer immunotherapies are demonstrating remarkable clinical activity in an increasing number of solid tumors and hematologic malignancies. Reliable biomarkers are needed to guide clinical decisions regarding treatment selection and identification of patients who are most likely to benefit. Testing for programmed death-ligand 1 (PD-L1) expression and the presence of DNA mismatch repair deficiencies (dMMR) or high levels of microsatellite instability (MSI-H) should presently be routinely done ...
Source: PeerView CME/CE Audio Podcast - Immunology - Category: Allergy & Immunology Authors: Tags: Science, Medicine Source Type: podcasts
Go online to PeerView.com/FQK860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. As a result of intense research efforts, the foundational understanding of the interplay between cancer and immunity and how to harness it for therapeutic benefit is deepening. As the evidence base grows exponentially, the treatment landscape is becoming more complicated, highlighting the need for precision approaches to maximize the potential of immuno-oncology. In this activity, based on a recent live symposium held in San Francisco, CA, experts in immuno-oncology explore the latest evidenc...
Source: PeerView CME/CE Audio Podcast - Immunology - Category: Allergy & Immunology Authors: Tags: Science, Medicine Source Type: podcasts
Conclusions Toxoplasma gondii infection induces a strong innate and adaptive immune response. While the innate immunity is important for controlling the early stages of the infection (Yarovinsky, 2014), the adaptive immunity is critical for restricting the parasite replication during the later stages (Gazzinelli et al., 1992). Amongst the adaptive immune subsets, CD8 T cells are the primary effector cells while CD4 T cells play an essential helper role to maintain long-term immunity (Casciotti et al., 2002). Notwithstanding, a robust CD8 T cell immunity induced during acute phase of infection, does not result in the total...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion and Perspectives Being exquisitely regulated by “writers,” “erasers,” and “readers,” additional repelled proteins or miRNAs, m6A modification relates to nearly any step of mRNA metabolism, as well as ncRNA processing and circRNA translation. There is compelling evidence suggesting that m6A modification is especially critical in a variety of pathologic and physiologic immune responses including T cell homeostasis and differentiation, inflammation, and type I interferon production. Further results have indicated that aberrancies of interferon and Th17 frequencies in systemic lu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we investigated the impact of the human ALK-F1174L mutation in vivo on sympathetic neuroblast differentiation using Sox10-Cre;LSL-ALK-F1174L mice. The aim was to improve our understanding of the implication of ALK deregulated signaling in the initial steps of NB genesis. Results ALK-F1174L Causes Embryonic Lethality When Expressed in NCCs Prior to SA Lineage Commitment To assess the impact of the human ALK-F1174L activating mutation on the development and differentiation of the SNS, Sox10-Cre;LSL-ALK-F1174L embryos were generated. This model allowed to restrict the expression of the ALK-F1174L variant to ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions Lymphatic vessels, like blood vessels, are a highly interactive surface for cells of the immune system, and through the use of chemokines and their receptors can coordinate key interactions. These pathways can control the entry and function of particular immune subsets in a number of pathological conditions. Nonetheless LECs have distinct patterns of chemokine secretion and expression of chemokine receptors that distinguish them from the blood vessel system and mediate distinct roles and responses. The abundance and diversity of the chemokine family point to the likelihood that a plethora of novel chemokine fu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
More News: Allergy & Immunology | Cancer | Cancer & Oncology | HIV AIDS | Immunotherapy | Study