Blocking senescence and tolerogenic function of dendritic cells induced by γδ Treg cells enhances tumor-specific immunity for cancer immunotherapy.

Background: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

Methods: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays.

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.

Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population.

Impact of Hospital Volume on Utilization of Minimally Invasive Surgery for Gastric Cancer.

Background: Minimally invasive surgery (MIS) for gastric cancer is increasingly performed. The purpose of this study is to evaluate trends in utilization of laparoscopic and robotic techniques compared to open surgery as well as utilization based on hospital volume.

Methods: We used the National Cancer Database to query patients who underwent gastrectomy from 2010 to 2017 for adenocarcinoma.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.

Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

Background: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not.

Objective: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions.

Methods: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma.

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum.

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

Unlabelled: National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time.

Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma.

Purpose: Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2).

Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy.

The functional state of T cells is a key determinant for effective antitumor immunity and immunotherapy. Cellular metabolism, including lipid metabolism, controls T cell differentiation, survival, and effector functions. Here, we report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers.

Effects of yoga on improving quality of life in patients with breast cancer: a meta-analysis of randomized controlled trials.

Background: Complications of breast cancer treatment can cause physical and psychosocial distress in patients. Yoga demonstrates substantial potential as a supportive therapy for patients with breast cancer. Our aim is to conduct a meta-analysis of randomized controlled trials to evaluate the effectiveness of yoga in enhancing the quality of life (QoL) of patients with breast cancer.

Oxidized Lipoproteins Promote Resistance to Cancer Immunotherapy Independent of Patient Obesity.

Antitumor immunity is impaired in obese mice. Mechanistic insight into this observation remains sparse and whether it is recapitulated in patients with cancer is unclear because clinical studies have produced conflicting and controversial findings. We addressed this by analyzing data from patients with a diverse array of cancer types.

Historic recombination in a durum wheat breeding panel enables high-resolution mapping of Fusarium head blight resistance quantitative trait loci.

The durum wheat line DT696 is a source of moderate Fusarium head blight (FHB) resistance. Previous analysis using a bi-parental population identified two FHB resistance quantitative trait loci (QTL) on chromosome 5A: 5A1 was co-located with a plant height QTL, and 5A2 with a major maturity QTL. A Genome-Wide Association Study (GWAS) of DT696 derivative lines from 72 crosses based on multi-environment FHB resistance, plant height, and maturity phenotypic data was conducted to improve the mapping resolution and further elucidate the genetic relationship of height and maturity with FHB resistance.

Molecular risk prediction in cutaneous melanoma: A meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients.

Background: Multiple studies have reported on the accuracy of the prognostic 31-gene expression profile test for cutaneous melanoma. Consistency of the test results across studies has not been systematically evaluated.

Objective: To assess the robustness of the prognostic value of the 31-gene expression profile.

Weighted gene co-expression network analysis unveils gene networks associated with the Fusarium head blight resistance in tetraploid wheat.

Background: Fusarium head blight (FHB) resistance in the durum wheat breeding gene pool is rarely reported. Triticum turgidum ssp. carthlicum line Blackbird is a tetraploid relative of durum wheat that offers partial FHB resistance.

Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging: Results From a Large Multicenter Trial.

Objective: To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging.

Background: It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low.

Methods: Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial.

Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma.

Background: Gene expression profiling (GEP) has been integrated into cancer treatment decision-making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31-GEP test (DecisionDx-Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB).

Methods: One hundred fifty-nine patients (age 26-88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing.

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

Aim: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?

Patients & Methods: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.

Results: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.

TLR8-Mediated Metabolic Control of Human Treg Function: A Mechanistic Target for Cancer Immunotherapy.

Regulatory T (Treg) cells induce an immunosuppressive microenvironment that is a major obstacle for successful tumor immunotherapy. Dissecting the regulatory mechanisms between energy metabolism and functionality in Treg cells will provide insight toward developing novel immunotherapies against cancer. Here we report that human naturally occurring and tumor-associated Treg cells exhibit distinct metabolic profiles with selectivity for glucose metabolism compared with effector T cells.

Cytoreductive Surgery and Normothermic Intraperitoneal Chemotherapy for Signet Ring Cell Appendiceal Adenocarcinoma With Peritoneal Metastases in the Setting of Cirrhosis.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal surface malignancies (PSM). The objective of cytoreduction is to eradicate macroscopic disease, while HIPEC addresses residual microscopic disease. Currently, there are no protocols guiding treatment of cirrhotic patients with PSM.

Review of diagnostic, prognostic, and predictive biomarkers in melanoma.

Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens.

SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex.

Background: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.

Methods: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate.

Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition.

Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion.