Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes

Sarter, Kerstin; Leimgruber, Elisa; Gobet, Florian; Agrawal, Vishal; Dunand-Sauthier, Isabelle; Barras, Emmanuèle; Mastelic-Gavillet, Béatris; Kamath, Arun T.; Fontannaz, Paola; Guéry, Leslie; Durães, Fernanda do Valle; Lippens, Carla; Ravn, Ulla; Santiago-Raber, Marie-Laure; Magistrelli, Giovanni; Fischer, Nicolas; Siegrist, Claire‐Anne; Hugues, Stéphanie; Reith, Walter

doi:10.1084/jem.20150435

Cited by 50 publications

(56 citation statements)

References 31 publications

(51 reference statements)

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“…Examining the association between the regulation of BTN and BTNL8 genes and the elevated levels of IL6 and IFNγ RNA revealed an inverse correlation between IFNγ and BTN3A3 (Supporting Information Figure S2) but no correlation between the pro‐inflammatory cytokines and the BTN1A1 , BTN2A2 , BTN3A2 or BTNL8 genes (data not shown). The association between the increased expression of BTN3A3 and decreasing IFNγ levels, as well as recent data that provide evidence that murine Btn2a2 is a co‐inhibitory molecule that negatively modulates T‐cell mediated immune responses , suggests that BTN molecules indeed may represent a feedback mechanism counteracting the effect of inflammation. Although a powerful immune response may be host‐protective, a tight regulation of the intestinal BTN and BTNL genes may be important for attenuating T‐cell mediated immune responses and thus for limiting tissue damage and progression to chronic inflammation.…”

Section: Resultsmentioning

confidence: 80%

“…Butyrophilin (BTN) and butyrophilin‐like (BTNL) proteins share significant homology and structural features with B7‐molecules and like B7‐molecules consist of regulatory molecules that modulate T‐cell mediated immune responses . Although T‐cell regulation by BTN and BTNL proteins is now unfolding, little is still known about the proteins' role in inflammation and proliferative disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Polymorphism in the human BTNL2 gene has been linked to inflammatory disorders such as sarcoidosis, ulcerative colitis (UC), rheumatoid arthritis and myositis , and to prostate cancer . Furthermore, over‐expression of Btnl2 has been reported in Mdr1a −/− mice, a mouse model of intestinal bowel disease , and Btn2a2 deficiency was recently described to potentiate anti‐tumor responses . Moreover, a few studies have identified an association between human BTN3 and ovarian cancer .…”

Section: Introductionmentioning

confidence: 99%

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Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer

Lebrero‐Fernández

Wenzel

Akéus

et al. 2016

Immunity Inflam & Disease

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Several Butyrophilin (BTN) and Btn‐like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real‐time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2 −/−) and intestinal tumorigenesis (Apc Min/+). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially BTN1A1, BTN2A2, BTN3A3, and BTNL8 were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of BTNL2, BTNL3, BTNL8, and BTNL9 as compared to unaffected tissue. Colonic inflammation in Muc2 −/− mice significantly down‐regulated the expression of particularly Btnl1, Btnl4, and Btnl6 mRNA, and intestinal polyps derived from Apc Min/+ mice displayed altered levels of Btn1a1, Btn2a2, and Btnl1 transcripts. Thus, our data present an association of BTN and BTNL genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.

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Section: Resultsmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer

Lebrero‐Fernández

Wenzel

Akéus

et al. 2016

Immunity Inflam & Disease

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“…Among the IgSF receptors, the CD28 family (CD28, ICOS, CTLA4, PD1, PD1H, and BTLA) and B7 family (B71, B7H1/PDL1) are the most well-described members. Additional IgSF cosignaling receptors—type I transmembrane immunoglobulin and mucin (TIM) domaincontaining molecules, CD2/signaling lymphocytic activation molecule (SLAM) family members, Butyrophilin (BTN) and BTN-like (BTNL) family molecules, Lymphocyte activation gene 3 protein (LAG3), and CD226 family members (CD226, CRTAM, TIGIT, and CD96)—have also been reported 44–47 . The TNFRSF receptors contain one or more extracellular cysteine-rich domain and are divided into 4 major subfamilies: Type-V (4–1BB, OX40, CD27, GITR, CD30); Type-L (TNFR1, TNFG2, HVEM, TNFRSF3, TNFRSF25, TNFRSF6B, FAS, CD40, RANK, OPG, TRAILR1–4); Type-S (TACI, BAFFR, BCMA, TWEAKR, EDAR); and orphan.…”

Section: Overview Of the Human Immune Systemmentioning

confidence: 99%

The challenges of checkpoint inhibition in the treatment of multiple myeloma

Paul

Kang

Zheng

et al. 2018

Cellular Immunology

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Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. While checkpoint inhibitors are effective in prolonging overall survival in some patients with advanced solid cancers and Hodgkin lymphoma, they have not demonstrated significant anti-myeloma activities as a single agent in MM. In fact the combination of checkpoint inhibitors with IMiDs was recently found to increase the risk of death in myeloma patients. These challenges highlight the need for a better understanding of immune dysregulation in myeloma patients, and the mechanisms of action of- and resistance to- checkpoint inhibitors. In this review, we summarize immune dysfunction in patients with MM, and review the preclinical and clinical data regarding checkpoint inhibitors in myeloma. We conclude by proposing strategies to improve the efficacy and safety of checkpoint inhibitors in this population.

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“…In this regard, 8 out of 19 cancer therapies that received FDA breakthrough status in 2015 were designed to improve antitumor immune responses. The identification of novel molecular immune checkpoints [1], along with innovative adoptive T cell transfer [2 • ,3] and dendritic cell vaccine protocols in clinical trials [4], as well as combinatorial approaches that utilize conventional immunotherapy [5], define immunotherapy as an evolving treatment option with the documented potential to eradicate metastatic malignancies.…”

Section: Elimination Of Antigen Expressing Tumors: a Common Link In Imentioning

confidence: 99%

Unmasking targets of antitumor immunity via high-throughput antigen profiling

Battaglia

Muhitch

2016

Current Opinion in Biotechnology

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More than three decades of evidence has established that antitumor immune responses, initially shown with IL-2 treatment, can result in complete, durable eradication of malignant disease in metastatic patients. Recent studies have demonstrated that immune checkpoint blockade as well as cellular therapies, including dendritic cell activation of T cells and adoptive T cell transfer, can induce long-lasting responses. To elicit cytolysis of tumor cells, effector T cells rely on tumor expression of target antigens. However, the antigens targeted during antitumor responses are largely unknown. Technological advancements and availability of sequencing data have paved the way for more efficient screening and validation of tumor-associated antigens and neoantigens derived from non-synonymous mutations targeted by T cells under baseline conditions and in the context of immunotherapy.

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Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes

Cited by 50 publications

References 31 publications

Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer

Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer

The challenges of checkpoint inhibition in the treatment of multiple myeloma

Unmasking targets of antitumor immunity via high-throughput antigen profiling

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