CD80 expression promotes immune surveillance in Barrett’s metaplasia

Scarpa, Melania; Fassan, Matteo; Kotsafti, Andromachi; Realdon, Stefano; Dall’Olmo, Luigi; Morbin, T.; Cavallin, Francesco; Saadeh, Luca Maria; Cagol, Matteo; Alfieri, Rita; Castoro, Carlo; Castagliuolo, Ignazio; Scarpa, Marco

doi:10.1080/2162402x.2019.1636618

Cited by 3 publications

(5 citation statements)

References 23 publications

(21 reference statements)

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“…6 It is upregulated upon cell stress and it is critical for efficacious immune surveillance during carcinogenesis. [7][8][9] Low surface expression of CD80 was reported as an immune escape mechanism of colon carcinoma; 10 on the other hand, its expression resulted enhanced in high-frequency microsatellite instability (MSI) colorectal cancers, a CRC subtype which is highly immunogenic and associated with a better prognosis. 11 Both in vivo and in vitro studies showed that the upregulation of CD80 on tumor cell surface successfully activates anti-tumor immune responses, while its expression is frequently lost during tumor progression probably due to selective pressure by the immune system.…”

Section: Introductionmentioning

confidence: 99%

CD80 expression is upregulated by TP53 activation in human cancer epithelial cells

et al. 2021

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CD80 is recognized as one of the most potent costimulatory molecules by which immune cells limit cancer progression; however, the current understanding of the regulation of its expression on human tumor cells is limited. The TP53 tumor suppressor plays a critical role in cancer and its significant role in the control of immune responses is emerging. Here, we evaluated the role of TP53 as a regulator of CD80 expression in human cancer cells. A set of well-known TP53–reactivating compounds were used on TP53-wild-type, TP53-deficient, TP53-mutated and TP53-knockdown cancer cell lines to determine if TP53 can regulate CD80. CD80 expression was analyzed in samples from patients with TP53-active vs TP53-inactive Colon Adenocarcinomas (COAD) from TCGA panCancer Atlas. We report that the pharmacological activation of TP53 can stimulate the expression of CD80 in human tumor cells of epithelial origin. We also provide evidence that CD80 expression exhibits a strong correlation with TP53 activation in a subgroup of colon tumors with better overall survival. These results confirm the link between TP53 and immune surveillance in human cancer and provide the possibility that conventional TP53-activation approaches for tumoricidal effects may be repurposed for immunotherapy strategies.

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Section: Introductionmentioning

confidence: 99%

CD80 expression is upregulated by TP53 activation in human cancer epithelial cells

et al. 2021

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“…The role of CD80 in esophageal carcinogenesis was observed and well demonstrated in our pervious study. 29 A high expression of CTLA4 in esophageal healthy tissue might in part compromise the antigen presentation and, thus, the lymphocyte activation that is necessary for the immune response elicited by radiotherapy. 30 On the other hand, CD8β is the marker of CD8 cytotoxic activation and low level of it was observed in patients with ulcerative colitis and who did not manage to eliminate low-grade dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Immune surveillance activation after neoadjuvant therapy for esophageal adenocarcinoma and complete response

et al. 2020

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After neoadjuvant chemoradiotherapy for esophageal adenocarcinoma, up to 29% of patients have a pathological complete response (pCR). What to do afterward is still under debate. The aim of this prospective study was to define which local markers of immune response might act as predictors of pCR and of recurrence after pCR. The peritumoral healthy mucosa of the surgical specimen was sampled at esophagectomy and analyzed by immunohistochemistry, flow cytometry and Real-Time PCR. One hundred and twenty-three patients received neoadjuvant therapy for esophageal adenocarcinoma and were included in the study. Significantly higher rate of natural killer (NK) cells (CD57+), intraepithelial CD8 + T lymphocytes and degranulating T-and NK-cells (CD107+) were observed in the healthy mucosa of patients with pCR. Moreover, pCR was characterized by a lower immune-check points gene expression level. T-cell activation markers mRNA levels were significantly lower in patients with pCR and recurrent disease, showing an excellent accuracy in the prediction of the postoperative recurrence. Costimulatory molecules mRNA relative levels tended to be lower in patients with pCR and recurrent disease, showing a good accuracy in the prediction of postoperative recurrence in patients with pCR. The immune profile identified in this study might further be tested in large prospective trials as marker of pCR after neoadjuvant therapy and as predictor of recurrence after pCR.

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“…Significant correlation between survival of ESCC patients and CTLA-4 + TIMCs density in EC TME was discovered [38] . Moreover, it is proved that CD80 plays a protective role during metaplasia in inflammatory esophageal carcinogenesis, which is closely related to EAC [40] …”

Section: Mechanisms Of Icis For the Treatment Of Ecmentioning

confidence: 94%

“…[38] Moreover, it is proved that CD80 plays a protective role during metaplasia in inflammatory esophageal carcinogenesis, which is closely related to EAC. [40] Given these findings, scientists designed ICIs targeting CTLA-4 to boost anti-tumor immunity for EC. How CTLA-4 blockade therapy affects effector T cells and EC TME awaits to be revealed.…”

Section: Pd-1 and Pd-l1mentioning

confidence: 99%

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Treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy

Yan

Feng

et al. 2022

Chinese Medical Journal

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Esophageal cancer (EC) has a high incidence and poor prognosis. The two major histological types, squamous cell carcinoma and adenocarcinoma, differ in their epidemiology and treatment options. Patients with locally advanced EC benefit from multimodal therapy concepts including neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy, and perioperative chemotherapy. Currently, immunotherapy for the solid tumor is a hot spot. Treatment with adjuvant immune checkpoint inhibitors (ICIs) is the first immunotherapy for resectable EC listed in the latest National Comprehensive Cancer Network Guidelines for the Esophageal and Esophagogastric Junction Cancers. Recent clinical trials have established ICIs for three treatment models of resectable EC. Their short-term results demonstrated ideal efficacy and tolerable toxicity, though some concerns remain. This review summarizes the novel data on the ICIs for resectable EC and lists the registered related clinical trials. Hopefully, this review can provide a reference for ongoing research on the treatment options for resectable EC.

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CD80 expression promotes immune surveillance in Barrett’s metaplasia

Cited by 3 publications

References 23 publications

CD80 expression is upregulated by TP53 activation in human cancer epithelial cells

CD80 expression is upregulated by TP53 activation in human cancer epithelial cells

Immune surveillance activation after neoadjuvant therapy for esophageal adenocarcinoma and complete response

Treatments for resectable esophageal cancer: from traditional systemic therapy to immunotherapy

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