CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma

Dakappagari, Naveen; Ho, Steffan N.; Gascoyne, Randy D.; Ranuio, Julie; Weng, Andrew P.; Tangri, Shabnam

doi:10.1002/cyto.b.20631

Cited by 22 publications

(14 citation statements)

References 19 publications

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“…Full activation of T cells requires binding of the CD28 receptor by CD80 or CD86 on antigen-presenting cells [ 38 ]. It was reported that CD80 is expressed in the majority of human DLBCL cases and is also present on nonmalignant stromal cells [ 39 ]. In contrast, one study revealed that acute lymphoblastic leukemia cells have low expression of costimulatory molecules including CD80 and suggested that this probably contributes to the absence of a host T cell-stimulated immune response [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma

et al. 2018

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B cell high grade lymphoma is the most common hematopoietic malignancy in dogs. Although the immune checkpoint molecules, programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and immune checkpoint inhibitors have been evaluated for the treatment of various human lymphoid malignancies, the expression of those molecules and their relationship with prognosis remain unknown in canine lymphoma. The objective of this study was to evaluate the expression of costimulatory molecules on peripheral blood lymphocytes and tumor infiltrating lymphocytes, in addition to associated ligand expression in the lymph nodes of patients with B cell multicentric high grade lymphoma. Eighteen patients diagnosed with B cell high grade lymphoma and nine healthy control dogs were enrolled. Flow cytometric analysis revealed that the expression of PD-1 on CD4+ peripheral and tumor infiltrating lymphocytes and CTLA-4 on CD4+ peripheral lymphocytes was significantly higher in the lymphoma group than in the control group. The expression level of CD80 mRNA was significantly lower in the lymphoma group than in the control group. In contrast, there were no significant differences in PD-L1, PD-L2, and CD86 expression between the groups. Dogs with CTLA-4 levels below the cutoff values, which were determined based on receiver operating characteristic curves, on peripheral CD4+, CD8+, and tumor infiltrating CD4+ lymphocytes had significantly longer survival than dogs with values above the cutoff. Although it is uncertain whether the expression of immune checkpoint molecules affect the biological behavior of canine lymphoma, one possible explanation is that PD-1 and CTLA-4 might be associated with the suppression of antitumor immunity in dogs with B cell high grade lymphoma, particularly through CD4+ T cells.

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Section: Discussionmentioning

confidence: 99%

Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma

et al. 2018

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“…Consistent with the high efficacy of PD-1 blockade in Hodgkin lymphoma, CD28 is strongly or moderately expressed on T cells surrounding CD80/CD86hi-expressing Reed-Sternberg cells ( 294 – 296 ). In contrast, chronic lymphocytic leukemia has no or low levels of CD80/CD86 expression on leukemia cells ( 297 – 299 ) with immunologic synapse formation defects ( 300 ) and is resistant to pembrolizumab in a clinical trial ( 224 ).…”

Section: Overcoming Resistance To Pd-1/pd-l1 Blockade: Various Combinmentioning

confidence: 99%

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

et al. 2017

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PD-1–PD-L1 interaction is known to drive T cell dysfunction, which can be blocked by anti-PD-1/PD-L1 antibodies. However, studies have also shown that the function of the PD-1–PD-L1 axis is affected by the complex immunologic regulation network, and some CD8+ T cells can enter an irreversible dysfunctional state that cannot be rescued by PD-1/PD-L1 blockade. In most advanced cancers, except Hodgkin lymphoma (which has high PD-L1/L2 expression) and melanoma (which has high tumor mutational burden), the objective response rate with anti-PD-1/PD-L1 monotherapy is only ~20%, and immune-related toxicities and hyperprogression can occur in a small subset of patients during PD-1/PD-L1 blockade therapy. The lack of efficacy in up to 80% of patients was not necessarily associated with negative PD-1 and PD-L1 expression, suggesting that the roles of PD-1/PD-L1 in immune suppression and the mechanisms of action of antibodies remain to be better defined. In addition, important immune regulatory mechanisms within or outside of the PD-1/PD-L1 network need to be discovered and targeted to increase the response rate and to reduce the toxicities of immune checkpoint blockade therapies. This paper reviews the major functional and clinical studies of PD-1/PD-L1, including those with discrepancies in the pathologic and biomarker role of PD-1 and PD-L1 and the effectiveness of PD-1/PD-L1 blockade. The goal is to improve understanding of the efficacy of PD-1/PD-L1 blockade immunotherapy, as well as enhance the development of therapeutic strategies to overcome the resistance mechanisms and unleash the antitumor immune response to combat cancer.

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“…Based on these observations one may conclude that the relative expression of B7‐1 and B7‐2 by malignant cells dictates the prognosis of hematological malignancies. Immune suppression through the interaction between B7‐1 expressed by malignant cells and nonmalignant cells with PD‐L1 has been shown to promote tumor progression in NHL . In this regard, it is likely that targeting this interaction will restore antitumour responses.…”

Section: B7 Ligands In Cancer and Autoimmunitymentioning

confidence: 99%

“…The interaction between B7‐1 and PD‐L1 in vitro provides an inhibitory signal, depicted by reduced T‐cell activation and cytokine production . Binding of PD‐L1 to B7‐1 provides another level of T‐cell regulation during antitumor responses and graft vs host disease . Interestingly, a few studies have demonstrated that PD‐L1 and B7‐1 can interact in cis on the same cell as a mechanism to block interaction with PD‐1 or CTLA‐4 and corresponding T‐cell inhibition .…”

Section: Introductionmentioning

confidence: 99%

Targeting B7‐1 in immunotherapy

Chen

Okoye

Arutyunova

et al. 2019

Medicinal Research Reviews

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Modulation of T‐cell immune functions by blocking key immune checkpoint protein interactions using monoclonal antibodies (mAbs) has been an innovative immunotherapeutic strategy. T‐cells are regulated by different checkpoint proteins at the immunological synapse including the B7 ligands (B7‐1 or CD80 and B7‐2 or CD86), which is discussed in this review. These ligands are typically expressed on antigen presenting cells and interact with CD28 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4) receptors on T‐cells. Their interactions with CD28 trigger a costimulatory signal that potentiates T‐cell activation, function and survival in response to cognate antigen. In addition, their interactions with CTLA‐4 can also inhibit certain effector T‐cell responses, particularly in response to sustained antigen stimulation. Through these mechanisms, the balance between T‐cell activation and suppression is maintained, preventing the occurrence of immunopathology. Given their crucial roles in immune regulation, targeting B7 ligands has been an attractive strategy in cancer and autoimmunity. This review presents an overview of the essential roles of B7‐1, highlighting the therapeutic benefits of modulating this protein in immunotherapy, and reviewing earlier and state‐of‐the‐art efforts in developing anti‐B7‐1 inhibitors. Finally, we discuss the challenges facing the design of selective B7‐1 inhibitors and present our perspectives for future developments.

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CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non‐Hodgkin lymphoma

Cited by 22 publications

References 19 publications

Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma

Evaluation of costimulatory molecules in dogs with B cell high grade lymphoma

PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response?

Targeting B7‐1 in immunotherapy

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