The B7 Homologues and their Receptors in Hematologic Malignancies

The B7 homologues and their receptors regulate both peripheral tolerance and adaptive immunity. This field is rapidly evolving as new ligands and receptors are being identified. Much of the work supporting their role in the regulation of host anti‐tumor immunity has been derived from experimental models and clinical trials in solid malignancies. However, a growing body of evidence demonstrates that the B7‐H family has important immunologic and non‐immunologic functions in a variety of hematologic malignancies. Herein, we will review recent evidence that supports the therapeutic targeting of the B7 homologues in hematologic malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91338/1/ejh1766.pd

Glycosylation of Immune Receptors in Cancer

Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor immune response, currently occupies a solid position in the rapidly expanding arsenal of cancer therapy. As most immune checkpoints are membrane glycoproteins, mounting attention is drawn to asking how protein glycosylation affects immune function. The answers to this fundamental question will stimulate the rational development of future cancer diagnostics and therapeutic strategies

The Inhibitory Role of B7-H4 in Antitumor Immunity: Association with Cancer Progression and Survival

B7-H4 is one of the most recently identified members of B7 superfamily of costimulatory molecules serving as an inhibitory modulator of T-cell response. B7-H4 is broadly expressed in human peripheral tissues and inducibly expressed in immune cells. The expression of B7-H4 has been observed in various types of human cancer tissues, and its soluble form has been detected in blood samples from cancer patients. However, its precise physiological role is still elusive, as its receptor has not been identified and the expression levels are not consistent. This paper summarizes the pertinent data on the inhibitory role of B7-H4 in antitumor immunity and its association with cancer progression and survival in human patients. The paper also discusses the clinical significance of investigating B7-H4 as potential markers for cancer diagnosis and prognosis, and as therapeutic targets

B7-H3 and Its Role in Antitumor Immunity

B7-H3 is one of the most recently identified members of the B7/CD28 superfamily of costimulatory molecules serving as an accessory modulator of T-cell response. Recently, B7-H3 expression has been reported in several human cancers indicating an additional function of B7-H3 as a regulator of antitumor immunity. However, its precise physiologic role is still elusive, because both stimulatory and inhibitory capacities have been demonstrated. This paper summarizes the available data on B7-H3 in the regulation of T-cell response focusing on its potential role in antitumor immunity

The inhibitory role of B7-H4 in antitumor immunity: association with cancer progression

B7-H4 is one of the most recently identified members of B7 superfamily of costimulatory molecules serving as an inhibitory modulator of T-cell response. B7-H4 is broadly expressed in human peripheral tissues and inducibly expressed in immune cells. The expression of B7-H4 has been observed in various types of human cancer tissues, and its soluble form has been detected in blood samples from cancer patients. However, its precise physiological role is still elusive, as its receptor has not been identified and the expression levels are not consistent. This paper summarizes the pertinent data on the inhibitory role of B7-H4 in antitumor immunity and its association with cancer progression and survival in human patients. The paper also discusses the clinical significance of investigating B7-H4 as potential markers for cancer diagnosis and prognosis, and as therapeutic targets

Association of b7-h4 gene polymorphisms in urothelial bladder cancer

Background/aim: We aimed to study polymorphisms of the B7-H4 gene in order to evaluate a possible association in urothelial carcinoma, as it is highly expressed in cancer tissues. Materials and methods: In this study B7-H4 gene rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a control group including 30 patients without bladder cancer. Results: We detected that the rs10754339 polymorphism was more frequent in the cancer patients when compared with the control group (P < 0.05). Only the rs3738414 polymorphism showed a statistically significant difference in frequency between pathologic diagnostic groups. Conclusion: The rs10754339 AA genotype distribution was found to have a higher frequency whereas the rs3738414 AG genotype distribution was lower in the bladder cancer group (P < 0.05). None of the genotype distributions showed a significant difference from the control group for the rs10801935 polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic marker in urothelial carcinoma

Costimulation in Allergic Asthma: The Roles of B7 and Semaphorin Molecules

It is well established that allergic asthma is T cell-driven disease where CD4+ T cells of Th2 phenotype play a critical role in disease initiation and maintenance. There are several critical steps in the induction of Th2 type immune response to the allergen. The first critical step is the antigen processing and presentation of allergen-derived peptides in the context of specific major histocompatibility Class II (MHCII) molecules by antigen-presenting cells (APC). Recognition of this complex by T cell receptor (TCR) and interaction of costimulatory ligands with corresponding receptors represents the second step in T cell activation. As the third part of optimal T cell differentiation, proliferation, and expansion, several cytokines, integrins, and chemokines get involved in the fine-tuning of DC-T cell interaction and activation. Multiple recent evidences point to the selected members of B7 and semaphorin families as important checkpoints providing a fine-tuning regulation of immune response. In this book chapter, we discuss the properties of costimulatory molecules and address their roles in allergic asthma