PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer.

Tumor-associated macrophages (TAMs) are the predominant cells that express programmed cell death ligand 1 (PD-L1) within human tumors in addition to cancer cells, and PD-L1 TAMs are generally thought to be immunosuppressive within the tumor immune microenvironment (TIME). Using single-cell transcriptomic and spatial multiplex immunofluorescence analyses, we show that PD-L1 TAMs are mature and immunostimulatory with spatial preference to T cells. In contrast, PD-L1 TAMs are immunosuppressive and spatially co-localize with cancer cells.

Baicalein activates 5' adenosine monophosphate-activated protein kinase, inhibits the mammalian target of rapamycin, and exhibits antiproliferative effects in pancreatic neuroendocrine tumors in vitro and in vivo.

Background: The mammalian target of rapamycin inhibition has been shown to prolong progression-free survival in patients with pancreatic neuroendocrine tumors. The natural compound baicalein indirectly inhibits the mammalian target of rapamycin, but it is unknown if baicalein exhibits such effects at physiologically achievable concentrations or exhibits synergy.

Methods: Pancreatic neuroendocrine tumor cell lines were cultured with baicalein, everolimus, and/or a synthetic 5' adenosine monophosphate-activated protein kinase activating agent alone and in combination.

Tumor-infiltrating exhausted CD8+ T cells dictate reduced survival in premenopausal estrogen receptor-positive breast cancer.

CD8+ tumor-infiltrating lymphocytes (TILs) are associated with improved survival in triple-negative breast cancer (TNBC) yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identified subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX).

Phase II Trial of Neoadjuvant Carboplatin and Nab-Paclitaxel in Patients with Triple-Negative Breast Cancer.

Background: In this phase II clinical trial, we evaluated the efficacy of the nonanthracycline combination of carboplatin and nab-paclitaxel in early stage triple-negative breast cancer (TNBC).

Patients And Methods: Patients with newly diagnosed stage II-III TNBC (n = 69) were treated with neoadjuvant carboplatin (area under the curve 6) every 28 days for four cycles plus nab-paclitaxel (100 mg/m ) weekly for 16 weeks. Pathological complete response (pCR) and residual cancer burden (RCB) were analyzed with germline mutation status, tumor-infiltrating lymphocytes (TILs), TNBC molecular subtype, and GeparSixto immune signature (GSIS).

Inhibition of Autophagy Amplifies Baicalein-Induced Apoptosis in Human Colorectal Cancer.

Baicalein is a Chinese herbal compound extracted from that has anti-tumor properties. The aim of this study was to elucidate the mechanisms of action of baicalein against human colorectal cancer cell lines and to assess whether the anti-proliferative effects of baicalein may be amplified with autophagy inhibition. Human colon cancer cell lines (HT-29, HCT-116, SW480, and SW620) were treated with baicalein alone and in combination with the autophagy inhibitor chloroquine (CQ).

Synergistic Anti-Tumor Activity by Targeting Multiple Signaling Pathways in Ovarian Cancer.

More effective therapy is needed to improve the survival of patients with advanced and recurrent ovarian cancer. Preclinical and early clinical studies with single molecular targeted agents have shown limited antitumor activity in ovarian cancer, likely due to compensation by alternative growth/survival pathways. An emerging strategy in overcoming resistance is to combine inhibitors targeting multiple pathways.

Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes.

Background: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients' peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease.

Insurance Status Predicts Survival in Women with Breast Cancer: Results of Breast and Cervical Cancer Treatment Program in California.

Background And Purpose: The Breast and Cervical Cancer Treatment Program (BCCTP) Act, passed by Congress in 2000, provides time-limited coverage to uninsured breast or cervical cancer patients. We examine survival differences between BCCTP cases and insured controls.

Methods: Stage I-III breast cancer patients, covered under California's BCCTP from 2005 to 2009 (N = 6343), were 1:1 matched with California Cancer Registry controls on age, race/ethnicity, and cancer stage.

Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer.

Background: Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC.

Eribulin Synergistically Increases Anti-Tumor Activity of an mTOR Inhibitor by Inhibiting pAKT/pS6K/pS6 in Triple Negative Breast Cancer.

Unlike other breast cancer subtypes, patients with triple negative breast cancer (TNBC) have poor outcomes and no effective targeted therapies, leaving an unmet need for therapeutic targets. Efforts to profile these tumors have revealed the PI3K/AKT/mTOR pathway as a potential target. Activation of this pathway also contributes to resistance to anti-cancer agents, including microtubule-targeting agents.

Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients.

CD8+ tumor-infiltrating lymphocytes (TILs) correlate with relapse-free survival (RFS) in most cancer types, including breast cancer. However, subset composition, functional status, and spatial location of CD8+ TILs in relation to RFS in human breast tumors remain unclear. Spatial tissue analysis via quantitative immunofluorescence showed that infiltration of CD8+ T cells into cancer islands was more significantly associated with RFS than CD8+ T cell infiltration into either tumor stroma or total tumor.

Differential gene expression and AKT targeting in triple negative breast cancer.

Metastatic triple negative breast cancer (mTNBC) is a heterogeneous disease with poor prognosis. Molecular evolution of TNBC through chemotherapy selection pressure is well recognized but poorly understood. PI3K/AKT/mTOR is one of the most commonly identified oncogenic-driver pathways in breast cancer.

Connecting blood and intratumoral T cell activity in predicting future relapse in breast cancer.

Regulatory T (T) cells play a major role in the development of an immunosuppressive tumor microenvironment. The origin of intratumoral T cells and their relationship with peripheral blood T cells remain unclear. T cells consist of at least three functionally distinct subpopulations.

Increasing Antitumor Activity of JAK Inhibitor by Simultaneous Blocking Multiple Survival Signaling Pathways in Human Ovarian Cancer.

Many signaling pathways, including the JAK/STAT3 pathway, are aberrantly activated and associated with ovarian cancer growth and progression. However, inhibition of STAT3 pathway alone was not sufficient to effectively block human ovarian cancer cell survival in vitro, which could be due to the activation and compensation of multiple survival pathways. In this study, we investigated a strategy that can enhance antitumor activity of JAK/STAT3 inhibitor by combining with inhibitors targeting other growth and survival pathways.

Combination therapy with BYL719 and LEE011 is synergistic and causes a greater suppression of p-S6 in triple negative breast cancer.

A third of patients with triple negative breast cancer (TNBC) have relapsed disease within 2-5 years from initial diagnosis, leaving an unmet need for therapeutic targets. TNBC frequently harbors alterations of the PI3K/AKT/mTOR pathway, but single agent PI3K/AKT/mTOR inhibitors have not shown marked efficacy. In this study, we investigated a strategy to improve efficacy of PI3K-α inhibitor BYL719 (alpelisib) in TNBC.

Human breast tumor-infiltrating CD8 T cells retain polyfunctionality despite PD-1 expression.

Functional CD8 T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8 tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state.

Sentinel lymph node B cells can predict disease-free survival in breast cancer patients.

Tumor invasion into draining lymph nodes, especially sentinel lymph nodes (SLNs), is a key determinant of prognosis and treatment in breast cancer as part of the TNM staging system. Using multicolor histology and quantitative image analysis, we quantified immune cells within SLNs from a discovery cohort of 76 breast cancer patients. We found statistically more in situ CD3 T cells in tumor negative vs.

Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics.

Purpose: Thyroid cancer is frequently difficult to diagnose due to an overlap of cytologic features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules.

Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer.

Treatment for ovarian cancer remains challenging despite a high initial response rate to first line platinum-taxane treatment. Most patients eventually experience recurrence and require further treatment. Persistent activation of STAT3 is associated with cancer growth and progression and is also involved in cell resistance to platinum and taxane treatment.

Age greater than 60 years portends a worse prognosis in patients with papillary thyroid cancer: should there be three age categories for staging?

Background: Age is an important prognostic factor in papillary thyroid cancer (PTC), with better survival observed in patients < 45 years of age, regardless of stage. Although the impact of increasing age on PTC-related survival is well-known, previous studies have focused on survival relative to age 45 years only. As the number of patients entering their 7th decade of life increases, PTC-related survival in this demographic becomes increasingly important.

Correction: Genomic mutation-driven metastatic breast cancer therapy: a single center experience.

[This corrects the article DOI: 10.18632/oncotarget.14476.

Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12.

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast.

Genomic mutation-driven metastatic breast cancer therapy: a single center experience.

Background: Next-Generation Sequencing (NGS) has made genomic mutation-driven therapy feasible for metastatic breast cancer (MBC) patients. We frequently submit tumor tissue from MBC patients for targeted NGS of tumor using the Illumina HiSeq 2000 platform (FoundationOne®, Foundation Medicine, MA). Herein, we report the results and clinical impact of this test in MBC patients.

IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer.

IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear.

Time to Treatment: Measuring Quality Breast Cancer Care.

Background: To optimize breast cancer care, several organizations have crafted guidelines to define best practices for treating breast cancer. In addition to recommended therapies, 'timeliness of treatment' has been proposed as a quality metric. Our study evaluates time to surgical treatment and its effect on overall survival (OS).