Immune checkpoint blockade therapy for esophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Harada K
PROVIDER: S-EPMC5864622 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC5906259 | biostudies-literature
Project description:Esophageal cancer is the seventh most common cancer, with an estimated 572,000 new cases, and the sixth most common cause of cancer-related deaths in 2018 with 509,000 annual worldwide deaths. Advanced esophageal squamous cell carcinoma (ESCC) is one of devastating tumors with a 5-year survival rate of less than 5% in patients with metastatic disease. Treatment options for patients with advanced ESCC are limited. Current guidelines recommend chemotherapy containing a platinum and a fluoropyrimidine agent as a first-line treatment. Recently, immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab, have demonstrated antitumor activity and clinical efficacy in patients with advanced ESCC that is refractory or intolerant to first-line chemotherapy. ICIs are game-changers that not only transformed oncological strategy but also have a wide range of clinical potential in combination with conventional cytotoxic chemotherapy and radiotherapy. There is still an urgent, unmet need for reliable treatment options to conquer this intractable disease.
| S-EPMC8692100 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD-L1 expression on tumors, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.
| S-EPMC7469863 | biostudies-literature
Project description:Esophageal cancer (EC) has the seventh highest incidence and the sixth highest mortality rate of any type of cancer worldwide. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 95% of EC patients. The main treatment for EC patients is surgery and/or chemoradiotherapy (CRT). A large proportion of EC patients are already at an advanced stage of the disease by the time they are diagnosed. In these cases, CRT is left as the only treatment choice, and the treatment outcome is poor. Immune checkpoint inhibitors (ICIs) can improve clinical response and patient survival of patient with many types of tumors through reactivating antitumor immune response. The study of ICIs in ESCC is relative delayed compared with that in other solid tumors. Recent results from clinical trials have demonstrated the safety and efficacy of ICIs either alone or combined with chemotherapy or chemoradiotherapy in ESCC patients. Accumulated evidences also have shown the improved treatment outcome was associated with PD-L1 expression, tumor DNA instability-induced tumor mutational burden (TMB), and drawing lymphocytes into the tumor. Based on these findings, ICIs combined with CRT or radiotherapy (RT) are the focus of ongoing studies. This review will summarize the recent progress in this field, especially the mechanism of ICIs used in ESCC, their clinical efficacy and toxicities, and potential biomarkers.
| S-EPMC7576075 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is one of the common malignant tumors in the world. More than half of patients with ESCC were detected in advanced or metastatic disease at the time of initial diagnosis and lost the opportunities of surgery. Currently, surgical resection, radiotherapy, and chemotherapy are most utilized in clinical practice, however, they are associated with limited survival benefits. Recognition of the limitation of traditional antitumor strategies prompt the development of new means to treat human cancer. In recent years, studies on immune checkpoint inhibitors (eg PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, etc.) in ESCC have shown promising results. In addition, the combination of immune checkpoint inhibitor and traditional antitumor strategies for ESCC has caused extensive interest, and the results are encouraging. Previous analysis indicated that tumor cell PD-L1 expression, tumor mutation load (TMB), microsatellite instability-high status (MSI-H), and other biomarkers have relatively correlated with the efficacy of immunotherapy. This review explores the recent studies investigating checkpoint inhibitors in ESCC.
| S-EPMC6677374 | biostudies-literature
Project description:BackgroundThe use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified.MethodsWe collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi-omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry.ResultsResults demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1high , odds ratio [95% confidence interval]: 0.31 [0.10-0.97], p = 0.044). Compared with COL19A1low patients, COL19A1high patients benefited more from neoadjuvant immunotherapy (p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence-free survival (p = 0.013), and overall survival (p = 0.056). Moreover, analysis of an immune-activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy.ConclusionsThe findings of this study provide insight into the optimal design of individual treatments for ESCC patients.
| S-EPMC10175035 | biostudies-literature
Project description:Immune checkpoint blockade (ICB) is the foundation of current first-line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long-lasting remissions. With the expanding arsenal of ICB-based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.
| S-EPMC8364550 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide. Current treatment options, even though potentially curative, have many limitations including a high rate of complications. Over the past few years immune checkpoint inhibitors (ICI) targeting cytotoxic lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) have changed treatment paradigms in many malignancies and are currently under investigation in HNSCC as well. Despite improvements in treatment outcomes and the implementation of combined modality approaches long-term survival rates in patients with locally advanced HNSCC remain suboptimal. Accumulating evidence suggests that under certain conditions, radiation may be delivered in conjunction with ICI to augment efficacy. In this review, we will discuss the immune modulating mechanisms of ICI and radiation, how changing the dose, fractionation, and field of radiation may alter the tumor microenvironment (TME), and how these two treatment modalities may work in concert to generate durable treatment responses against HNSCC.
| S-EPMC6414812 | biostudies-literature
Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.
| S-EPMC7730197 | biostudies-literature
Project description:Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.
| S-EPMC4491954 | biostudies-literature