Dataset Information

Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

ABSTRACT: The incidence rates of vulvar squamous cell cancer (VSCC) have increased over the past decades, requiring personalized oncologic approaches. Currently, lymph node involvement is a key factor in determining prognosis and treatment options. However, there is a need for additional immune-related biomarkers to provide more precise treatment and prognostic information. Here, we used IHC and expression data to characterize immune cells and their spatial distribution in VSCC. Hierarchical clustering analysis identified distinct immune subtypes, of which the macrophage-rich subtype was associated with adverse outcome. This is consistent with our findings of increased lymphogenesis, lymphatic invasion, and lymph node involvement associated with high macrophage infiltration. Further in vitro studies showed that VSCC-associated macrophages expressed VEGF-A and subsequently induced VEGF-A in the VSCC cell line A-431, providing experimental support for a pro-lymphangiogenic role of macrophages in VSCC. Taken together, immune profiling in VSCC revealed tumor processes, identified a subset of patients with adverse outcome, and provided a valuable biomarker for risk stratification and therapeutic decision making for anti-VEGF treatment, ultimately contributing to the advancement of precision medicine in VSCC.

Significance

Immunoprofiling in VSCC reveals subtypes with distinct clinical and biological behavior. Of these, the macrophage-rich VSCC subtype is characterized by poor clinical outcome and increased VEGF-A expression, providing a biomarker for risk stratification and therapeutic sensitivity.

SUBMITTER: Condic M

PROVIDER: S-EPMC10956503 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

Condic Mateja M Rohr Andrea A Riemann Soheila S Staerk Christian C Ayub Tiyasha H TH Doeser Anna A Zillinger Thomas T Merkelbach-Bruse Sabine S Buettner Reinhard R Barchet Winfried W Rudlowski Christian C Mustea Alexander A Kübler Kirsten K

Cancer research communications 20240301 3

The incidence rates of vulvar squamous cell cancer (VSCC) have increased over the past decades, requiring personalized oncologic approaches. Currently, lymph node involvement is a key factor in determining prognosis and treatment options. However, there is a need for additional immune-related biomarkers to provide more precise treatment and prognostic information. Here, we used IHC and expression data to characterize immune cells and their spatial distribution in VSCC. Hierarchical clustering an ...[more]

PMID: 38407373

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Project description:BackgroundVulvar squamous cell carcinoma (VSCC) is a relatively rare gynecologic cancer. Unlike cervical squamous cell carcinoma (CSCC), in which nearly all cases are caused by HPV infection, most VSCCs are HPV-independent. Patients with VSCC also have worse overall survival (OS) than those with CSCC. Unlike CSCC, the risk factors of VSCC have not been extensively studied. Here, we investigated the prognostic values of clinicopathological parameters as well as biomarkers in patients with VSCC.MethodsIn total, 69 cases of VSCC accessions were selected for analysis between April 2010 and October 2020. The risk factors of VSCC were screened using Cox models to establish nomograms for predicting survival outcomes.ResultsFollowing the multivariate COX model for OS, independent predictors including advanced age (hazard ratio [HR] 5.899, p = 0.009), HPV positivity (HR 0.092, p = 0.016), high Ki-67 index (HR 7.899, p = 0.006), PD-L1-positivity (HR 4.736, p = 0.077), and CD8 + tumor-infiltrating lymphocytes (TILs) (HR 0.214, p = 0.024) were included in the nomogram for OS; multivariate COX model for progression-free survival (PFS) was used to screen prognostic factors including advanced age (HR 2.902, p = 0.058), lymph node metastasis (HR 5.038, p = 0.056), HPV positivity (HR 0.116, p = 0.011), high Ki-67 index (HR 3.680, p = 0.042), PD-L1-positivity (HR 5.311, p = 0.045), and CD8 + TILs (HR 0.236, p = 0.014) to establish the PFS nomogram model. Based on the C-index (0.754 for OS and 0.754 for PFS) from our VSCC cohort and the corrected C-index (0.699 for OS and 0.683 for PFS) from an internal validation cohort, the nomograms demonstrated good predictive and discriminative ability. Kaplan-Meier curves also supported the excellent performance of the nomograms.ConclusionOur prognostic nomograms suggested that (1) shorter OS and PFS were associated with PD-L1-positivity, high Ki-67 index, and low CD8 + TILs; (2) HPV-independent tumors were associated with poorer survival outcome, and mutant p53 status showed no prognostic significance.

Project description:BackgroundThe Immunoscore method, based on the distribution of the quantification of cytotoxic and memory T cells, provides an indicator of tumor recurrence for colon cancer. However, recent evidence has suggested that immune checkpoint expression represents a surrogate measure of tumor-infiltrating T cell exhaustion, and therefore may serve as a more accurate prognostic biomarker for colon cancer. Indoleamine 2, 3-dioxygenase 1 (IDO1), a potent immunosuppressive molecule, has been strongly associated with T-cell infiltration, but it lacks universal prognostic significance among all of the cancer subtypes. Our aim was to elucidate the prognostic significance of the combination of IDO1 and CD8A expression in colon cancer.MethodsGene expression and clinical survival data were analyzed using The Cancer Genome Atlas (TCGA) data set and validated using NCBI Gene Expression Omnibus (NCBI-GEO) cohort. Hierarchical clustering, functional enrichment analyses, and immune infiltration analysis were applied to evaluate the distinctive immune statuses in colon cancer risk subgroups stratified by IDO1 and CD8A expression. Moreover, Multivariate Cox regression analysis and Receiver Operating Characteristic (ROC) analyses were conducted to determine the prognostic value of IDO1/CD8A stratification. The IDO1/CD8A classifier may be suitable for use in the prediction of cancer development. It was validated via an in vivo murine model.ResultsThe stratification analysis demonstrated that the colon cancer subtype with the CD8AhighIDO1high* tumor resulted in the worst survival despite high levels of CD8 infiltrates. Its poor prognosis was associated with high levels of immune response, checkpoint genes, and Th1/IFN-γ gene signatures, regardless of CMS classification. Moreover, the IDO1/CD8A stratification was identified as an independent prognostic factor of overall survival (OS) and a useful predictive biomarker in colon cancer. In vivo data revealed the CD8AhighIDO1high group showed strong correlations with late-stage metastasis of colon carcinoma cells and upregulation of immune checkpoints.ConclusionsThe findings indicate that the proposed IDO1/CD8A stratification has exact and independent prognostic implications beyond CD8 T cell alone and CMS classification. As a result, it may represent a promising tool for risk stratification in colon cancer and improve the development of immunotherapies for patients with colon cancer in the future.

Dataset Information

Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

Significance

Publications

Immune Profiling of Vulvar Squamous Cell Cancer Discovers a Macrophage-rich Subtype Associated with Poor Prognosis.

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