798P A phase II study of pembrolizumab (P) in combination with doxorubicin (D) in advanced endometrial cancer (AEC): TOPIC trial/VHIO10001

Fariñas‐Madrid, Lorena; Rubio, María Jesús; Redondo, Andrés; Javierre, G. Villacampa; Esteban, Alfonso Yubero; Romero, Ignacio; Gil-Martín, Marta; García-Donás, Jesús; González-Martín, Antonio; Martínez, Antonio; Grau, F.; Ruiz-Pace, Fiorella; Burdaló, B. Pardo; Lorenzo, Maria Luisa Sanchez; Piulats, Josep M.; Oaknin, Ana

doi:10.1016/j.annonc.2021.08.1240

Cited by 3 publications

(1 citation statement)

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“…Combined immunotherapy has shown potential in providing better survival outcomes for advanced patients: Pembrolizumab in combination with Lenvatinib has significantly improved the objective response rate (ORR) and long-term survival in UCEC patients with disease progression [ 8 – 11 ]. In addition to the anti-angiogenic drugs, the combination of immunotherapy and chemotherapy is being explored as well, with Pembrolizumab combined with doxorubicin being shown to exert substantial anti-tumor activity and controllable safety in advanced UCEC patients who did not respond to platinum-based chemotherapy [ 12 ]. Thus, immunotherapy is assuming an increasingly important role in the remedy of UCEC.…”

Section: Introductionmentioning

confidence: 99%

Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma

et al. 2023

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Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. Methods CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. Results Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. Conclusions In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.

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Section: Introductionmentioning

confidence: 99%

Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma

et al. 2023

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Facts and Hopes in Immunotherapy of Endometrial Cancer

Marín-Jiménez

García-Mulero

Matías‐Guiu

et al. 2022

Clinical Cancer Research

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Immunotherapy with checkpoint inhibitors has changed the paradigm of treatment for many tumors, and endometrial carcinoma is not an exception. Approved treatment options are pembrolizumab or dostarlimab for mismatch repair deficient tumors, pembrolizumab for tumors with high mutational load, and, more recently, pembrolizumab/lenvatinib for all endometrial cancer patients. Endometrial cancer is a heterogeneous disease with distinct molecular subtypes and different prognoses. Differences between molecular subgroups regarding antigenicity and immunogenicity should be relevant to develop more tailored immun-therapeutic approaches. In this review, we aim to summarize and discuss the current evidence -Facts-, and future opportunities -Hopes- of immunotherapy for endometrial cancer focusing on relevant molecular and tumor microenvironment features of The Cancer Genome Atlas endometrial cancer subtypes.

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Construction of the Novel Immune Risk Scoring System Related to CD8 + T Cells in Uterine Corpus Endometrial Carcinoma

Zhang

Yin

Fang

et al. 2023

Preprint

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Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought huge survival benefits for some specific patients, the traditional evaluation indicators cannot accurately identify all beneficiaries. To construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy, key genes related to CD8+T cells and prognosis were selected out to develop the novel immune risk score (NIRS). Subsequently, correlations between NIRS and other prognostic features such as clinical characteristics, microsatellite status, immune infiltration and tumor mutation burden were investigated. Five module genes (GPR18, CD48, LCK, LTA, and SLAMF1) were selected to construct NIRS after multiple screening procedures. NIRS is considered as an independent prognostic factor of UCEC. The increase in NIRS is accompanied by decreases in infiltrated immune cells and immune checkpoint expression; thus, indicating a lower sensibility to immune checkpoint inhibitors. Five module genes were considered protective factors and positively linked to the level of CD8+ T cells by single gene multi-omics analyses. In this research, we constructed NIRS as a novel prognostic signature of UCEC. NIRS can not only distinguish patients with different prognoses and immune responsiveness, but also guide their therapeutic regimens.

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798P A phase II study of pembrolizumab (P) in combination with doxorubicin (D) in advanced endometrial cancer (AEC): TOPIC trial/VHIO10001

Cited by 3 publications

References 0 publications

Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma

Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma

Facts and Hopes in Immunotherapy of Endometrial Cancer

Construction of the Novel Immune Risk Scoring System Related to CD8 + T Cells in Uterine Corpus Endometrial Carcinoma

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