Dataset Information

Dynamic alteration and prognostic significance of tumor-associated CD68⁺ and CD68⁺ PD-L1^- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

ABSTRACT:

Background

The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC).

Methods

Multiplex immunofluorescence staining was performed to examine CD68⁺ TAM, CD4⁺ T cell, CD8⁺ T cell, FOXP3⁺ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR).

Results

There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68⁺ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68⁺ PD-L1^- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68⁺ PD-L1⁺ and TILs. The infiltration of CD68⁺ (p = 0.033), CD68⁺ PD-L1^- (p = 0.033), and CD68⁺ PD-L1⁺ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients.

Conclusion

CD68⁺ and CD68⁺ PD-L1^- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.

SUBMITTER: Wu J

PROVIDER: S-EPMC9972069 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Dynamic alteration and prognostic significance of tumor-associated CD68<sup>+</sup> and CD68<sup>+</sup> PD-L1<sup>-</sup> macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

Wu Jie J Xie Rui-Yang RY Wei Li-Hui LH Cao Chuan-Zhen CZ Shang Bing-Qing BQ Guan You-Yan YY Shi Hong-Zhe HZ Qu Wang W Li Yun Y Liang Jing J Zheng Shan S Zhou Ai-Ping AP Zhou Xiao-Feng XF Shou Jian-Zhong JZ Bi Xin-Gang XG

Cancer medicine 20220831 4

<h4>Background</h4>The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC).<h4>Methods</h4>Multiplex immunofluorescence staining was performed to examine CD68<sup>+</sup> TAM, CD4<sup>+</sup> T cell, CD8<sup>+</sup> T cell, FOXP3<sup>+</sup> Treg cell, and PD-L1 expres ...[more]

PMID: 36043478

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Project description:IntroductionThis meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma (MIBC).Materials and methodsFour databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade≥ 3 irAEs rate, RFS, and OS were performed.ResultsIn total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30-0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95%CI=0.19-0.35, p=0.1), 0.41 (95%CI=0.21-0.62, p=0.01), 0.43 (95%CI=0.35-0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46-0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22-0.51, p=0.01), 0.51 (95%CI=0.39-0.62, p=0.43), and 0.61 (95%CI=0.53-0.69, p=0.01), respectively. Kaplan-Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade≥ 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95%CI=0.09-0.22, p=0.00%). In subgroup analysis, the pooled result of Grade≥ 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04-0.11, p=0.84), 0.31 (95%CI=0.16-0.47, p=0.06), and 0.17 (95%CI=0.06-0.31, I2 = 71.27%, p=0.01), respectively.ConclusionNeoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade≥3 irAEs. Kaplan-Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452437, identifier PROSPERO (CRD42023452437).

Project description:BackgroundNon-muscle-invasive bladder cancer (NMIBC) is over three times as common in men as it is in women; however, female patients do not respond as well to immunotherapeutic treatments and experience worse clinical outcomes than their male counterparts. Based on the established sexual dimorphism in mucosal immune responses, we hypothesized that the tumor immune microenvironment of bladder cancer differs between the sexes, and this may contribute to discrepancies in clinical outcomes.ObjectiveTo determine biological sex-associated differences in the expression of immune regulatory genes and spatial organization of immune cells in tumors from NMIBC patients.Design setting and participantsImmune regulatory gene expression levels in tumors from male (n = 357) and female (n = 103) patients were measured using whole transcriptome profiles of tumors from the UROMOL cohort. Multiplexe immunofluorescence was performed to evaluate the density and spatial distribution of immune cells and immune checkpoints in tumors from an independent cohort of patients with NMIBC (n = 259 males and n = 73 females).Outcome measurements and statistical analysisTranscriptome sequencing data were analyzed using DESeq2 in R v4.0.1, followed by application of the Kruskal-Wallis test to determine gene expression differences between tumors from males and females. Immunofluorescence data analyses were conducted using R version 3.5.3. Survival analysis was performed using survminer packages.Results and limitationsHigh-grade tumors from female patients exhibited significantly increased expression of B-cell recruitment (CXCL13) and function (CD40)-associated genes and the immune checkpoint genes CTLA4, PDCD1, LAG3, and ICOS. Tumors from female patients showed significantly higher infiltration of PD-L1+ cells and CD163+ M2-like macrophages than tumors from male patients. Increased abundance of CD163+ macrophages and CD79a+ B cells were associated with decreased recurrence-free survival.ConclusionsThese novel findings highlight the necessity of considering sexual dimorphism in the design of future immunotherapy trials in NMIBC.Patient summaryIn this study, we measured the abundance of various immune cell types between tumors from male and female patients with non-muscle-invasive bladder cancer. We demonstrate that tumors from female patients have a significantly higher abundance of immunosuppressive macrophages that express CD163. Higher abundance of tumor-associated CD163-expressing macrophages and B cells is associated with shorter recurrence-free survival in both male and female patients.

Dataset Information

Dynamic alteration and prognostic significance of tumor-associated CD68⁺ and CD68⁺ PD-L1^- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

Background

Methods

Results

Conclusion

Publications

Dynamic alteration and prognostic significance of tumor-associated CD68<sup>+</sup> and CD68<sup>+</sup> PD-L1<sup>-</sup> macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Dynamic alteration and prognostic significance of tumor-associated CD68+ and CD68+ PD-L1- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

Background

Methods

Results

Conclusion

Publications

Dynamic alteration and prognostic significance of tumor-associated CD68<sup>+</sup> and CD68<sup>+</sup> PD-L1<sup>-</sup> macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dynamic alteration and prognostic significance of tumor-associated CD68⁺ and CD68⁺ PD-L1^- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.