Dataset Information

Integrating molecular subtype and CD8⁺ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

ABSTRACT:

Background

Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8⁺ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8⁺ T cells infiltration in MIBC.

Methods

This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8⁺ T cells and probed into the clinical implications of these subgroups in MIBC.

Results

Among patients with Luminal-CD8⁺T^high tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8⁺T^low displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8⁺T^low subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8⁺T^high counterparts exhibited a heightened responsiveness to chemotherapy.

Conclusions

We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.

SUBMITTER: Li B

PROVIDER: S-EPMC10908619 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Integrating molecular subtype and CD8<sup>+</sup> T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

Li Bingyu B Jin Kaifeng K Liu Zhaopei Z Su Xiaohe X Xu Ziyue Z Liu Ge G Xu Jingtong J Liu Hailong H Chang Yuan Y Wang Yiwei Y Zhu Yu Y Wang Zewei Z Xu Le L Zhang Weijuan W

Cancer immunology, immunotherapy : CII 20240302 4

<h4>Background</h4>Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8<sup>+</sup> T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8<sup>+</sup> T cells infiltration in MIBC.<h4>Methods</h4>This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigo ...[more]

PMID: 38430246

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Project description:Muscle-invasive urothelial bladder cancer (MIBC) is associated with limited response rates to systemic therapy, risk of recurrence and death. Tumor infiltrating immune cells have been associated with outcome and response to chemo-and immunotherapy in MIBC. We aimed to profile the immune cells in the tumor microenvironment (TME) to predict prognosis in MIBC and responses to adjuvant chemotherapy. We performed multiplex immunohistochemistry (IHC) profiling and quantification of immune and stromal cells (CD3, CD4, CD8, CD163, FoxP3, PD-1, and CD45, Vimentin, αSMA, PD-L1, Pan-Cytokeratin, Ki67) in 101 patients with MIBC receiving radical cystectomy. We used uni- and multivariate survival analyses to identify cell types predicting prognosis. Samples were subdivided using K-means clustering for Treg and macrophage infiltration resulting in 3 clusters, Cluster 1: Treg high, cluster 2: macrophage high, cluster 3: Treg and macrophage low. Routine CD68 and CD163 IHC were analyzed with QuPath in an extended cohort of 141 MIBC. High concentrations of macrophages were associated with increased risk of death (HR 10.9, 95% CI 2.8-40.5; p < 0.001) and high concentrations of Tregs were associated with decreased risk of death (HR 0.1, 95% CI 0.01-0.7; p = 0.03) in the multivariate Cox-regression model adjusting for adjuvant chemotherapy, tumor and lymph node stage. Patients in the macrophage rich cluster (2) showed the worst OS with and without adjuvant chemotherapy. The Treg rich cluster (1) showed high levels of effector and proliferating immune cells and had the best survival. Cluster 1 and 2 both were rich in PD-1 and PD-L1 expression on tumor and immune cells. Treg and macrophage concentrations in MIBC are independent predictors of prognosis and are important players in the TME. Standard IHC with CD163 for macrophages is feasible to predict prognosis but validation to use immune-cell infiltration, especially to predict response to systemic therapies, is required.

Project description:BackgroundThe gold standard treatment for localized muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy with radical cystectomy (RC). Guidelines suggest concurrent chemoradiation (CRT) could be considered as an alternative, and partial cystectomy (PC) may be considered in carefully selected individuals. The bladder preservation strategies are gaining popularity, and due to the concerns about morbidity associated with RC and limited life expectancy, the octogenarian population is exploring strategies that help preserve bladder function. Hence, it is crucial to understand the outcome of various bladder preservation strategies. Using the National Cancer Database (NCDB), we compared the overall survival (OS) of octogenarians treated with PC and CRT.MethodsWe retrospectively evaluated the octogenarians with localized MIBC (cT2N0M0) ≤5 cm and urothelial histology between 2004 and 2018. Our analytic cohorts were the PC cohort, which included patients who underwent PC, and the CRT cohort, which included patients who received chemotherapy and radiotherapy within a 90-day timeframe. After propensity-matching with race and ethnicity, gender, facility type, median income, comorbidity index, and tumor grade, we compared the OS between PC and CRT cohorts.ResultsA total of 1,038 were octogenarians who met our selection criteria. Among them, 248 (23.8%) underwent PC, and 790 (76.2%) received CRT. In the PC cohort, tumors were located predominantly in the dome (34.3%) and anterior wall (10.5%), while in the CRT cohort, tumors were in the trigone (8.4%), lateral (22.0%) and posterior walls (10.6%). The median OS for the matched PC and CRT cohort was 38.3 and 32.9 months, respectively (P=0.66). Multivariate Cox regression showed no difference in survival hazards between PC and CRT [hazard ratio =1.07 (95% confidence interval: 0.82-1.39)] (P=0.63).ConclusionsOur study comparing PC and CRT in octogenarians with T2 ≤5 cm tumors showed that PC had comparable OS to CRT. Therefore, PC can be considered a viable option in carefully selected octogenarians.

Dataset Information

Integrating molecular subtype and CD8⁺ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

Background

Methods

Results

Conclusions

Publications

Integrating molecular subtype and CD8<sup>+</sup> T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

Background

Methods

Results

Conclusions

Publications

Integrating molecular subtype and CD8<sup>+</sup> T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Integrating molecular subtype and CD8⁺ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.