Biological Landscape of Triple Negative Breast Cancers Expressing CTLA-4

Navarrete-Bernal, María G. C.; Cervantes-Badillo, Mayte Guadalupe; Martínez-Herrera, José Fabián; Lara-Torres, César; Gerson-Cwilich, Raquel; Zentella‐Dehesa, Alejandro; Ibarra-Sánchez, Marı́a de Jesús; Esparza-López, José; Montesinos, Juan José; Cortés-Morales, Víctor Adrián; Osorio-Pérez, Diego; Villegas-Osorno, Diana A.; Reyes-Sánchez, Eduardo; Salazar-Sojo, Pablo; Tallabs-Utrilla, Luis F.; Romero-Córdoba, Sandra; Rocha‐Zavaleta, Leticia

doi:10.3389/fonc.2020.01206

Cited by 33 publications

(27 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Potential biologic and therapeutic insights may also be gleaned from CTLA-4, an immune checkpoint protein expressed on T-cell subsets, which was significantly decreased in PD-L1 + stromal TIME, compared with PD-L1 − tumors. As reported, 50%–70% of TNBC express CTLA-4 ( 46 , 47 ), this observation may reflect differential CTLA-4–expressing and PD-L1–expressing TIME in TNBC, or an overall paucity of CTLA-4 in PD-L1 + tumors. Early clinical data of combined anti-PD-L1 (nivolumab) and anti-CTLA-4 therapy (ipilimumab) in the phase II DART trial has shown promise in a small set of patients with advanced metaplastic breast carcinoma ( 48 ).…”

Section: Discussionmentioning

confidence: 54%

Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

Carter

Polley

Leon‐Ferre

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

Relevance PD-(L)1-targeted immunotherapies have shown modest survival benefit in advanced TNBC and improved pathological response in the neoadjuvant setting. Using the FDA-approved PD-L1 SP142 and 22C3 companion assays, we identified clinicopathological characteristics, RNA-based immune features and spatially-constrained protein-based tumor immune microenvironments (TIME) of early-stage PD-L1+ TNBC. 46% of TNBC were PD-L1+ with the SP142 assay, and 16% were PD-L1+ with the 22C3 assay. PD-L1+ TNBC were higher grade and had higher tumor-infiltrating lymphocytes (TILs). With deconvolution of RNA data, PD-L1+ TNBC had increased dendritic cell, macrophage, and lymphocytic immune features, with decreased myeloid-derived suppressor cells. By high-plex digital spatial profiling, PD-L1+ stroma and intraepithelial tumor TIME were highly enriched in IDO-1, HLA-DR, CD40 and CD163, and had TIMEspecific alterations in functionally-diverse immune proteins (CTLA-4, STING, fibronectin). These data provide biologic insight and identify candidate targets for future studies of combinatorial immunotherapies in patients with PD-L1+ TNBC.Research.

show abstract

Section: Discussionmentioning

confidence: 54%

Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

Carter

Polley

Leon‐Ferre

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Two breast cancer cell lines (MDA-MB-231 and HCC1937) were selected. MDA-MB-231 cells resemble a mesenchymal phenotype similar to MBCDF-D5 cells by expressing vimentin, and HCC1937 cells express E-cadherin similar to MBCDF cells ( 31 ). MDA-MB-231, HCC-1937, MBCDF and MBCDF-D5 cells were treated with increasing doses of paclitaxel (0, 0.05, 0.1, 0.5, 1, 5, 10 and 25 µg/ml; Fig.…”

Section: Resultsmentioning

confidence: 99%

Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells

et al. 2021

View full text Add to dashboard Cite

Paclitaxel has been used widely to treat breast cancer and other types of cancer. However, resistance is a major cause of failure for treatment and results in cancer progression. The present study investigated the association between paclitaxel resistance and the mesenchymal phenotype, using a model of primary breast cancer cells and employing four different cultures, two with an epithelial phenotype (MBCDF and MBCD17) and two with a mesenchymal phenotype (MBCDF-D5 and MBCD3). Epithelial-mesenchymal markers were evaluated by western blotting; MBCDF and MBCD17 cells expressed E-cadherin, SNAIL, Slug, and Twist, low levels of N-cadherin, but not vimentin. MBCDF-D5 and MBCD3 cells expressed N-cadherin, vimentin, and higher levels of SNAIL, and low levels of E-cadherin, Slug, and Twist. Cell viability was evaluated using a crystal violet assay after paclitaxel treatment; primary breast cancer cells with mesenchymal phenotype were resistant to paclitaxel compared with the epithelial primary breast cancer cells. Furthermore, using western blotting, it was revealed that mesenchymal cells had elevated levels of nuclear factor-κΒ (NF-κB) p65 and IκB kinase (IKK). Additionally, it was demonstrated that paclitaxel-induced degradation of the inhibitor of NF-κB, activation of NF-κB in a dose-dependent manner, and Bcl-2 and Bcl-xL upregulation. Finally, employing western blotting and crystal violet assays, the effects of the proteasome inhibitor ALLN were assessed. ALLN inhibited paclitaxel-induced NF-κB activation and restored the sensitivity to paclitaxel. Together, these data suggest that targeting the NF-κB/IKK axis might be a promising strategy to overcome paclitaxel resistance.

show abstract

“…breast cancer, however its clinical meaning needs to be elucidated. 24,25 The finding that high CTLA-4 expression is associated with worse histological response in patients with bevacizumab-pretreated colorectal liver metastases suggests that CTLA-4 may be an additional target in a multidisciplinary treatment approach.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases

Stift

Gráf

Neudert

et al. 2022

HPB

View full text Add to dashboard Cite

Background: The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study.Methods: Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated.Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively.Results: One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001).Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases. Conclusion:Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.

show abstract

Biological Landscape of Triple Negative Breast Cancers Expressing CTLA-4

Cited by 33 publications

References 85 publications

Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

Characteristics and Spatially Defined Immune (micro)landscapes of Early-stage PD-L1–positive Triple-negative Breast Cancer

Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells

Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases

Contact Info

Product

Resources

About