Introducing a New Series: Immunotherapy Facts and Hopes

Melero, Ignacio; Sznol, Mario; Tessmer, Marlowe S.; Whiteside, Theresa L.; Wolchok, Jedd D.

doi:10.1158/1078-0432.ccr-18-0408

Cited by 4 publications

(3 citation statements)

References 8 publications

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“…[1][2][3][4][5] The 5-year survival rate of patients with advanced-stage OSCC has improved minimally over the last 30 years. 6 Immune checkpoint inhibitors (ICIs) in advanced-stage OSCC have shown therapeutic benefit for a minority of patients [7][8][9][10] ; however, the utility of ICI in OSCC may be limited, in part, to genomic alterations in tumor that contribute to an immunosuppressive tumor immune microenvironment (TIME). One such candidate alteration is TP53 mutation, which occurs in 75%-85% of HNSCC cases, including OSCC.…”

Section: Open Accessmentioning

confidence: 99%

TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma

Shi,

Ren,

Cao

et al. 2023

J Immunother Cancer

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BackgroundTP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. SomaticTP53mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role ofTP53gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.MethodsShort hairpin RNA knockdown of mutantp53R172Hin syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutantp53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutantp53R172Hin the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level.ResultsMutantp53R172Hcontributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover,p53R172Halso regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly,p53R172H-mutated tumors are infiltrated with CD8+and CD4+T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and theTP53R175Hmutation, which paralleled the findings from our syngeneic mouse tumor model.ConclusionsThese findings demonstrate that syngeneic tumors bearing theTP53R172Hgain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.

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Section: Open Accessmentioning

confidence: 99%

TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma

Shi,

Ren,

Cao

et al. 2023

J Immunother Cancer

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“…At the end of 2016, nearly 60 antibody drugs had been approved by the Food and Drug Administration, and many more are currently in clinical trials . Recently, bioengineered bispecific antibodies (BsAbs) containing two different binding sites within a single molecule seem to offer the potential to improve therapeutic efficacy and promise to be the next generation of immunotherapy. , From this perspective, it would be extremely important to be able to measure, during immunotherapy treatment, the levels of therapeutic antibodies at designated time intervals and to maintain a constant drug concentration in a patient’s bloodstream, thereby optimizing individual dosage regimens and clinical outcomes in patients. − For the reasons mentioned above, point-of-care (POC) methods for the detection and quantification of therapeutic antibodies would improve the characterization and monitoring of immunotherapies, improving their efficacy with subsequent great societal and medical benefits.…”

Section: Optical Structure-switching Dna Scaffoldsmentioning

confidence: 99%

DNA-Based Scaffolds for Sensing Applications

2018

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“…Other than cetuximab and nivolumab, no new targeted therapies or biomarkers have been approved for HNSCC (Jie et al 2015;Ward-Hartstonge and Kemp 2017). This complex disease may be effectively targeted by immunotherapy once better understanding of the disease microenvironment is obtained (Melero et al 2018). Understanding host cell signaling and identifying immune infiltrates can reveal novel approaches for cancer therapeutics (Li and Rudensky 2016).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of Helios, Neuropilin-1 and FoxP3 in head and neck squamous cell carcinoma (HNSCC) patients

et al. 2019

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In recent years, studies have begun to explore the immune involvement in head and neck tumors. Advanced stage head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with low survival rates with high level of immune infiltrates. Tregs (regulatory T cells) play a crucial role in constructing an immunosuppressive tumor microenvironment. In the present study, we highlighted specific Treg markers and its factors in HNSCC solid tumors and peripheral blood of cancer patients. By histopathology and immunofluorescence staining, we observed differential expression of CD4, CD25, Foxp3, Helios and Neuropilin-1. Further, we analyzed the expression of Foxp3, Helios, Neuropilin-1 and GARP by qPCR and flow cytometry in whole blood and found to be elevated in HNSCC patients in comparison with healthy donors. Additionally, IFN-γ, TGF-β, IL-6, IL-2, IL-10 and TNF-α expressions were also found to be relatively increased in the head and neck cancer patients when compared with healthy donors. Our findings emphasize that Tregs may be involved in promoting tumor progression. Helios and Neuropilin-1 could be potent markers in identifying subsets of Tregs. Association of soluble factors could sculpture the activity of Tregs. With further research, Treg markers and its associated soluble factors could be employed to block Tregs trafficking to the tumor, thus enlightening a potential strategy for targeting human cancers.

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Introducing a New Series: Immunotherapy Facts and Hopes

Cited by 4 publications

References 8 publications

TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma

TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma

DNA-Based Scaffolds for Sensing Applications

Differential expression of Helios, Neuropilin-1 and FoxP3 in head and neck squamous cell carcinoma (HNSCC) patients

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