Unmasking targets of antitumor immunity via high-throughput antigen profiling

Battaglia, Sebastiano; Muhitch, Jason B.

doi:10.1016/j.copbio.2016.03.001

Cited by 9 publications

(11 citation statements)

References 54 publications

(70 reference statements)

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“…In conclusion, our findings reveal that B7‐H5/CD28H is a co‐stimulatory signal pathway, and expression of B7‐H5 is associated with improved disease prognosis in PDAC, which indicate that the B7‐H5/CD28H pathway might be a potential immunotherapeutic target in pancreatic cancer. Although there are no available agents to target B7‐H5 or CD28H currently, the success of limited number of immunotherapeutic studies on pancreatic cancer has provided considerable evidence with space for improvement . Combined with standard chemotherapy or other immunotherapy strategies, targeting the B7‐H5/CD28H pathway may be an effective treatment approach for pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

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B7‐H5/CD28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma

et al. 2019

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B7‐H5 and its cognate receptor CD28H are T lymphocyte second signaling transduction molecules. Here we aimed to explore the function of this pathway in pancreatic cancer in vitro and in vivo, and evaluated the clinical significance in 136 patients with pancreatic ductal adenocarcinoma enrolled from January 2012 to February 2017 in our hospital. Surgical tumor specimens were collected for immunohistochemical staining to evaluate B7‐H5 expression. Patients’ baseline characteristics, including gender, age, tumor size, tumor location, tumor grading, clinical TNM staging, tumor infiltrating lymphocytes, CA19‐9 and chemotherapy treatment, along with the subsequent follow‐up data, were documented and analyzed. When co‐cultured with T cells, pancreatic cancer PC cells with high B7‐H5 expression induced a more potent immune reaction, indicated by elevated cytokine release and increased proliferation of T lymphocytes compared with cells exhibiting low B7‐H5 expression. Xenograft pancreatic tumors derived from high B7‐H5 expression PC cells exhibited attenuated growth compared to tumors from low B7‐H5 expression cells after transfusion with T lymphocytes in immune‐deficient mice. Of the 136 PDAC tumor tissues, 93 (68.38%) were strong and 43 (31.62%) were weak B7‐H5 expression. Patients with strong B7‐H5 expression had significantly longer overall survival than those with weak expression (median: 16.5 vs 11.5 months, P = .017). TNM staging, tumor location and subsequent chemotherapy were also prognostic factors in these patients. Collectively, B7‐H5/CD28H is a co‐stimulatory signal pathway, and expression of B7‐H5 is associated with improved disease prognosis in patients with pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

“…Multivariable COX survival analysis considerable evidence with space for improvement 25. Combined with standard chemotherapy or other immunotherapy strategies, targeting the B7-H5/CD28H pathway may be an effective treatment approach for pancreatic cancer.…”

mentioning

confidence: 99%

B7‐H5/CD28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma

et al. 2019

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“…For example, hybrid peptides derived from two different proteins can occur via transpeptidation under conditions of endoplasmic reticulum stress, and will sometimes be the focus of an autoimmune response . Similarly, for tumor‐specific immunity, responses against tumor may be a result of neoantigen formation via somatic mutations in cancer cells that would be absent in the thymus . In addition to neoantigens, proteins, whose expression is spatially and/or temporally restricted, and can thus escape central and peripheral tolerance mechanisms, are well validated as targets of adaptive immune responses in both autoimmunity and cancer.…”

Section: Innate Immune Contributions To the Phases Of Autoimmune Pathmentioning

confidence: 99%

Breaking self-tolerance during autoimmunity and cancer immunity: Myeloid cells and type I IFN response regulation

Tarbell

Egen

2018

Journal of Leukocyte Biology

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The generation and regulation of innate immune signals are key determinants of autoimmune pathogenesis. Emerging evidence suggests that parallel processes operating in the setting of solid tumors can similarly determine the balance between tolerance and immunity and ultimately the effectiveness of the antitumor immune response. In both contexts, self-specific responses start with innate immune cell activation that leads to the initial break in self-tolerance, which can be followed by immune response amplification and maturation through innate-adaptive crosstalk, and finally immune-mediated tissue/tumor destruction that can further potentiate inflammation. Of particular importance for these processes is type I IFN, which is induced in response to endogenous ligands, such as self-nucleic acids, and acts on myeloid cells to promote the expansion of autoreactive or tumor-specific T cells and their influx into the target tissue. Evidence from the study of human disease pathophysiology and genetics and mouse models of disease has revealed an extensive and complex network of negative regulatory pathways that has evolved to restrain type I IFN production and activity. Here, we review the overlapping features of self- and tumor-specific immune responses, including the central role that regulators of the type I IFN response and innate immune cell activation play in maintaining tolerance, and discuss how a better understanding of the pathophysiology of autoimmunity can help to identify new approaches to promote immune-mediated tumor destruction.

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“…However, the antigens to be targeted for optimal antitumor immunity still need to be investigated. Advancement in technology, structural proteomics and information from sequencing data have enabled more efficient screening and validation of tumor-associated antigens (TAAs) that may be targeted by T cells (Battaglia and Muhitch, 2016). For instance, the understanding of the structure of tumor antigen p53, in ovarian cancer, led to the design of an effective p53 peptide inhibitor (Soragni et al, 2016).…”

Section: T Cell Receptorsmentioning

confidence: 99%

“…Structural understanding of TAAs recognized by effector T cells and design of therapies based on the TCR-pMHC interaction could be useful in combination with ACT. Molecular identification of human TAAs and their surface interaction with T cells should benefit targeted antigen-specific immunotherapy for cancer (Battaglia and Muhitch, 2016).…”

Section: T Cell Receptorsmentioning

confidence: 99%

Adoptive immunotherapy via CD4+ versus CD8+ T cells

Phan-Lai

2016

Biomed Res Ther

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Abstract-The goal of cancer immunotherapy is to induce specific and durable antitumor immunity. Adoptive T cell therapy (ACT) has garnered wide interest, particularly in regard to strategies to improve T cell efficacy in trials. There are many types of T cells (and subsets) which can be selected for use in ACT. CD4+ T cells are critical for the regulation, activation and aid of host defense mechanisms and, importantly, for enhancing the function of tumor-specific CD8+ T cells. To date, much research in cancer immunotherapy has focused on CD8+ T cells, in melanoma and other cancers. Both CD4+ T cells and CD8+ T cells have been evaluated as ACT in mice and humans, and both are effective at eliciting antitumor responses. IL-17 producing CD4+ T cells are a new subset of CD4+ T cells to be evaluated in ACT models. This review discusses the benefits of adoptive immunotherapy mediated by CD8+ and CD4+ cells. It also discusses the various type of T cells, source of T cells, and ex vivo cytokine growth factors for augmenting clinical efficacy of ACT.

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Unmasking targets of antitumor immunity via high-throughput antigen profiling

Cited by 9 publications

References 54 publications

B7‐H5/CD28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma

B7‐H5/CD28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma

Breaking self-tolerance during autoimmunity and cancer immunity: Myeloid cells and type I IFN response regulation

Adoptive immunotherapy via CD4+ versus CD8+ T cells

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