Facts and Hopes in Immunotherapy of Endometrial Cancer

Marín-Jiménez, Juan A.; García-Mulero, Sandra; Matías‐Guiu, Xavier; Piulats, Josep María

doi:10.1158/1078-0432.ccr-21-1564

Cited by 30 publications

(16 citation statements)

References 93 publications

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“…Since its processes and effects were discovered in the last ten years, tumor immunotherapy has become a novel therapeutic technique in cancer research [ 26 ]. Much of the research in the field of ICIs has been centered around PD-1 and PD-L1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer

Wan,

Huang,

Huang

et al. 2024

Discov Onc

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Background Studies evaluating the effectiveness of immune checkpoint inhibitors (ICI) for endometrial cancer (EC) are limited. This study aimed to assess the efficacy of PD-1/PD-L1 inhibitors as monotherapy for EC by conducting a meta-analysis. The predictive significance of MMR status, a biomarker for ICI response, also required further investigation. Methods A systematic literature search was conducted in English databases until September 2023. The analysis included objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and odds ratios (OR), along with their corresponding 95% confidence intervals (CI). Results There were twelve trials totaling 685 individuals. PD-1/PD-L1 inhibitor monotherapy resulted in an ORR for 34% (95% CI = 24–44%) of the pooled EC patients. Subgroup analysis revealed a significantly higher ORR in dMMR EC (45%) compared to pMMR EC (8%), with an OR of 6.36 (95% CI = 3.64–11.13). The overall DCR was 42%, with dMMR EC at 51% and pMMR EC at 30% (OR = 2.61, 95% CI = 1.69–4.05). Grade three or higher adverse events (AEs) occurred in 15% of cases (95% CI = 9–24%) of the pooled incidence of AEs, which was 68% (95% CI = 65–72%). Conclusions This meta-analysis provides significant evidence for the effectiveness of PD-1/PD-L1 inhibitors as monotherapy for EC. Notably, dMMR EC patients demonstrated superior treatment efficacy with PD-1/PD-L1 inhibitor immunotherapy. Further research is required to explore subclassifications of EC based on dMMR molecular subtypes, enabling improved treatment strategies and outcomes for EC patients.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer

Wan,

Huang,

Huang

et al. 2024

Discov Onc

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“…[5,10] Significant progress has been achieved in combining immunogenic and novel immunotherapeutic therapies for human cancers, [14] including EC. [15] However, the association of ICD with EC remains elusive. To this end, this study investigated the possible association between ICDRGs and EC via a series of bioinformatic analyses.…”

Section: Discussionmentioning

confidence: 99%

Identification of immunogenic cell death-related subtypes used for predicting survival and immunotherapy of endometrial carcinoma through a bioinformatics analysis

Liu

Luo

et al. 2023

Medicine

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Immunogenic cell death (ICD) is a unique phenomenon that can trigger comprehensive, adaptive immune responses through damage-associated molecular patterns, offering a promising avenue for tumor immunotherapy. However, the role of ICD-related genes and their correlation with endometrial carcinoma (EC), the most prevalent gynecologic malignancy, remains unclear. This study examined genetic, transcriptional, and clinical data of EC obtained from the Cancer Genome Atlas database. Unsupervised clustering analysis was utilized to identify distinct ICD clusters based on the expression of ICD-related genes. Regarding the different clusters, their survival analysis, assessment of the immune microenvironment, immune cell infiltration, immune checkpoint analysis, and tumor mutation burden analysis were performed. Furthermore, an ICD risk signature was established using univariate Cox regression and least absolute shrinkage and selection operator analysis. The Chi-square test was employed to investigate the relationship between the ICD score and clinical features. Multiple computational analytical tools were used to assess immune annotation, somatic mutations, tumor mutation burden, and response to immunotherapy and chemotherapy drugs in different ICD score groups. Two ICD clusters were identified, indicating that the ICD-high cluster was associated with improved prognosis, abundant immune cell infiltration, and enrichment of pathways related to immunologic activation. Moreover, the ICD risk signature showed predictive value for the immune microenvironment, immunotherapy response, chemotherapy susceptibility, and prognosis in EC. Our findings offer novel insights into personalized treatment strategies for EC patients.

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“…These tumors are characterized by microsatellite instability (MSI-H) and deficient MMR, and frequently by high tumor mutational burden. Due to this characteristic, these tumors are commonly more sensitive than MMR-proficient tumors to immunotherapy, such as checkpoint inhibitors including pembrolizumab, and more recently nivolumab, dostarlimab, and avelumab [ 7 ]. Much more commonly, an epigenetic abnormality such as MLH1 promoter hypermethylation underlies the MSI-H and deficient MMR findings, characteristic of many endometrioid carcinomas of the endometrium, as well as the dedifferentiated endometrial carcinoma.…”

Section: Deficient Mismatch Repair and Immuno-oncologymentioning

confidence: 99%

Advances in Chemotherapy and Targeted Therapies in Endometrial Cancer

Chambers

2022

Cancers

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Endometrial cancer is now recognized to be several diseases with differing biology and responses to treatment. Improved molecular characterization has furthered the development and testing of targeted therapies in the different cohorts of endometrial cancer. Lessons are being learned from other cancers that share similar molecular typing, and hence, potentially similar tumor behavior. This commentary serves as a broad overview of the types of advances to which our patients now have access.

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Facts and Hopes in Immunotherapy of Endometrial Cancer

Cited by 30 publications

References 93 publications

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer

Identification of immunogenic cell death-related subtypes used for predicting survival and immunotherapy of endometrial carcinoma through a bioinformatics analysis

Advances in Chemotherapy and Targeted Therapies in Endometrial Cancer

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