B7-H7 Is Inducible on T Cells to Regulate Their Immune Response and Serves as a Marker for Exhaustion

Luu, Khang; Schwarz, Herbert; Lundqvist, Andreas

doi:10.3389/fimmu.2021.682627

Cited by 10 publications

(4 citation statements)

References 40 publications

(43 reference statements)

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“…The aberrant highly expressed B7 members were correlated with poor prognosis in AML [ 12 ], and the PD-1 expression in CD8 + T cells was independently predictive of poor overall survival and event-free survival in AML patients [ 32 ]. Accordingly, induced expression of B7-H1 and B7-H7 on U937/Ara-C may dampen NK and T-cell function [ 34 – 36 ]. Moreover, B7-H1 on tumors also interacts with CD80 on T cell, inhibiting T cell responses in vivo [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members

Ge,

Yin,

Sun

et al. 2024

Discov Onc

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Acute myeloid leukemia (AML) remains challenging due to chemotherapeutic drug-resistance (CDR). Aberrant expression B7 family proteins are involved in tumors evasion. We wonder whether B7 family protein alteration in AML CDR further supports tumor escape. Here, we establish AML cytarabine-resistant cell line U937/Ara-C and report on the expression MHC molecule and B7 family member. HLA-ABC was highly expressed similarly on both cell lines. MIC (MHC class I chain related) A/B and B7-H6 was moderately expressed on the surface of U937 and decreased dramatically by U937/Ara-C. In contrast, enhanced expression of B7-H1 and B7-H7 by U937/Ara-C was observed. HLA-DR and other B7 family members including CD80, CD86, B7-DC, B7-H2, B7-H3, B7-H4, and B7-H5 were not detected by both cell lines. Compared co-cultured with U937, peripheral blood mononuclear cells showed a decreased cytotoxicity when incubated with U937/Ara-C, as indicated by decreased levels of granzyme B and perforin production, accompanied with less TNF-α and lactate dehydrogenase secretion. In conclusion, AML CDR further evades the anti-tumor immune response which may through MHC molecule and B7 family members.

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Section: Discussionmentioning

confidence: 99%

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members

Ge,

Yin,

Sun

et al. 2024

Discov Onc

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“…Zhao et al noted that as a suppressive immune checkpoint molecule, HHLA2 blocks the proliferation of CD4 and CD8 T cells and the synthesis of cytokines such as IFN-γ, TNF-α, IL-5, and IL-10 [ 138 ]. Recent studies have shown that HHLA2 is induced to be expressed only when T cells are activated and is preferentially expressed on CD8 T cells after activation, which may be related to the fact that HHLA2 can inhibit the cytotoxic effects of CD8 T cells faster and more strongly [ 141 ]. HHLA2/CD28H has been established to activate human T cells and generate cytokines including IFN-γ, TNF-α, IL-5, and IL-10 through the AKT pathway [ 137 ].…”

Section: Hhla2mentioning

confidence: 99%

“…The function of HHLA2 as a suppressive and stimulatory immune checkpoint in TME may be related to the predominance of different receptor interactions in different cancer types. Intriguingly, one study suggested that HHLA2 may be a better marker of T cell exhaustion than PD-1 [ 40 , 141 ].…”

Section: Hhla2mentioning

confidence: 99%

B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy

Chen

et al. 2022

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5–10%. The immune checkpoint blockade represented by PD-1/PD-L1 inhibitors has been effective in a variety of solid tumors but has had little clinical response in pancreatic cancer patients. The unique suppressive immune microenvironment is the primary reason for this outcome, and it is essential to identify key targets to remodel the immune microenvironment. Some B7 family immune checkpoints, particularly PD-L1, PD-L2, B7-H3, B7-H4, VISTA and HHLA2, have been identified as playing a significant role in the control of tumor immune responses. This paper provides a comprehensive overview of the recent research progress of some members of the B7 family in pancreatic cancer, which revealed that they can be involved in tumor progression through immune-dependent and non-immune-dependent pathways, highlighting the mechanisms of their involvement in tumor immune escape and assessing the prospects of their clinical application. Targeting B7 family immune checkpoints is expected to result in novel immunotherapeutic treatments for patients with pancreatic cancer.

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“…B7H7 exhibits both co-inhibitory and co-stimulatory properties on T lymphocytes [29]. In a study by Luu et al, it has been shown that B7H7 has a predominant expression by exhausted cytotoxic T lymphocytes (CTLs) and T helper 1 cells, which have impaired production of Tumor necrosis factor (TNF)-α and IFN-γ production [30]. In another study on NK-92MI and Jurkat T cells, it was revealed that an alternative receptor for B7H7 on T cells and NK cells is KIR3DL3 (Killer Cell Immunoglobulin Like Receptor), a protein containing three Ig domains with a long cytoplasmic tail.…”

Section: Introductionmentioning

confidence: 99%

siRNA-Mediated B7H7 Knockdown in Gastric Cancer Lysate-Loaded Dendritic Cells Amplifies Expansion and Cytokine Secretion of Autologous T Cells

Masoumi,

Ghorbaninezhad,

Saeedi

et al. 2023

Biomedicines

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Background: Gastric cancer, ranked as the fifth most common cancer worldwide, presents multiple treatment challenges. These obstacles often arise due to cancer stem cells, which are associated with recurrence, metastasis, and drug resistance. While dendritic cell (DC)-based immunotherapy has shown promise as a therapeutic strategy, its efficacy can be limited by the tumor microenvironment and certain inhibitory immune checkpoint molecules, such as B7H7. SiRNA-medicated knockdown of B7H7 in tumor cell lysate-pulsed DCs can increase cytokine secretion and autologous T lymphocyte expansion. This study aimed to evaluate the impact of B7H7 suppression in gastric cancer cell lysate-pulsed DCs on the stimulatory potential of autologous CD3+ T lymphocytes. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated and monocytes were obtained; then, they were differentiated to immature DCs (iDCs) by GM-CSF and IL-4. Tumor cell lysates from human gastric cancer cell lines were harvested, and iDCs were transformed into mature DCs (mDCs) by stimulating iDCs with tumor cell lysate and lipopolysaccharide. B7H7-siRNA was delivered into mDCs using electroporation, and gene silencing efficiency was assessed. The phenotypic characteristics of iDCs, mDCs, and B7H7-silenced mDCs were evaluated using specific surface markers, an inverted light microscope, and flow cytometry. CD3+ T cells were isolated via magnetically activated cell sorting. They were labeled with CFSE dye and co-cultured with mDCs and B7H7-silenced mDCs to evaluate their ability to induce T-cell proliferation. T-cell proliferation was assessed using flow cytometry. The concentration of TGF-β, IL-4, and IFN-γ secreted from CD3+ T cells in the co-cultured supernatant was evaluated to investigate the cytokine secretory activity of the cells. Results: Transfection of B7H7 siRNA into mDCs was performed in optimal conditions, and the siRNA transfection effectively reduced B7H7 mRNA expression in a dose-dependent manner. SiRNA-mediated B7H7 knockdown in mDCs enhanced maturation and activation of the DCs, as demonstrated by an increased surface expression of CD11c, CD86, and CD40. Co-culture experiments revealed that B7H7-silenced mDCs had more capacity to induce T cell proliferation compared to non-transfected mDCs. The cytokine production patterns of T cells were also altered. Upon examining the levels of TGF-β, IL-4, and IFN-γ released by CD3+ T cells in the co-culture supernatant, we found that silencing B7H7 in mDCs resulted in a rise in IL-4 secretion and a reduction in TGF-β levels compared to mDCs that were not transfected. Conclusions: The study found that suppressing B7H7 expression in DCs significantly enhances their maturation and stimulatory activity when exposed to gastric cancer cell lysate. These B7H7-silenced DCs can substantially increase cytokine production and promote co-cultured T-cell expansion. Consequently, inhibiting B7H7 in DCs may offer a practical strategy to enhance the ability of DCs to initiate T lymphocyte responses and improve the effectiveness of DC-based cell therapy for cancer patients.

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B7-H7 Is Inducible on T Cells to Regulate Their Immune Response and Serves as a Marker for Exhaustion

Cited by 10 publications

References 40 publications

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members

B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy

siRNA-Mediated B7H7 Knockdown in Gastric Cancer Lysate-Loaded Dendritic Cells Amplifies Expansion and Cytokine Secretion of Autologous T Cells

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