Dataset Information

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.

ABSTRACT: BACKGROUND:Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1). METHODS:CD4+, CD8+, FOXP3+, CTLA4+, PD-L1+ and PD-1+ expression was examined by immunohistochemistry on tissue microarrays (TMAs) from 180 BC patients. Univariate and Kaplan-Meier analyses of disease free survival (DFS) were performed to evaluate the prognostic significance of marker expression. RESULTS:Total CD8+ T cells were not significantly associated with DFS. Differently, patients with iCD8+ and sCD8+ overexpression showed a trend toward respectively a worse (P?=?.050) and a better 5-years DFS (P?=?.064). Interestingly, TIL expression of both PD-1+ and PD-L1+, was significantly associated with iCD8+ (P?=?.0004; P?

SUBMITTER: Catacchio I

PROVIDER: S-EPMC6350084 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.

Catacchio Ivana I Silvestris Nicola N Scarpi Emanuela E Schirosi Laura L Scattone Anna A Mangia Anita A

Translational oncology 20190122 3

<h4>Background</h4>Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stroma ...[more]

PMID: 30682679

Similar Datasets

Project description:So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients' survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-κB signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-κB inhibitor C-DIM 12 (3,3'-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough.

Project description:PurposeInvasive breast carcinoma (BC) is the most common malignant breast tumor. Most lymph node-negative (LN-) early-stage BC patients usually have a good prognosis, but 7% of patients still develop metastasis after surgery. It is not yet clear how to screen candidates with poorer prognosis in LN- early-stage patients, so that they can receive intensive therapy. Hence, we expect to identify a prognostic biomarker to assess postoperative metastasis in LN- early-stage BC patients.Patients and methodsScreening and verifying of candidate genes by gene expression profiling of LN- early-stage BC samples (n = 640) from 3 independent public datasets. Univariable and multivariable Cox regression analyses showed the relation between the candidate genes and postoperative metastasis. Distant metastasis-free survival (DMFS) analysis was performed to examine the prognostic significance. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine ADAMTS8 expression and prognostic association in our clinical samples (n = 25).ResultsIn the discovery cohort (TCGA and GSE20685 datasets), we found that ADAMTS8 tend to be low expression in LN- early-stage BC, and low ADAMTS8 expression was associated with postoperative metastasis and shortened DMFS. Moreover, the above finding was confirmed in the validation cohort (GSE6538 dataset). Lower ADAMTS8 expression was related to poorer prognostic clinical stage and PAM50 subtypes and shorter DMFS. Gene enrichment analysis indicated that ADAMTS8 may be correlated with BC metastasis. qRT-PCR assays of our clinical tumor sample showed that patients with low ADAMTS8 expression seem to be prone to developing metastasis and have a shorter DMFS time.ConclusionOur research shows that low ADAMTS8 expression is associated with postoperative metastasis and shortened DMFS in LN- early-stage BC patients, which suggests that ADAMTS8 may be a potential prognostic marker for postoperative metastasis in LN- early-stage BC patients.

Dataset Information

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.

Publications

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets