XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.

DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma.

Unlabelled: Neutrophil extracellular traps (NET), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that DNA of NETs (NET-DNA) binds transmembrane and coiled-coil domains 6 (TMCO6) on CD8+ T cells to impair antitumor immunity and thereby promote HCC progression.

The efficacy and safety of the combination of axitinib and pembrolizumab-activated autologous DC-CIK cell immunotherapy for patients with advanced renal cell carcinoma: a phase 2 study.

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab-activated autologous dendritic cells-co-cultured cytokine-induced killer cells in patients with advanced RCC.

Methods: All adult patients, including treatment-naive or pretreated with VEGF-targeted agents, were enrolled from May 2016 to March 2019.

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection.

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC.

Retrospective analysis of the efficacy of cytokine-induced killer cell immunotherapy combined with first-line chemotherapy in patients with metastatic colorectal cancer.

Objectives: Fluoropyrimidine-based chemotherapy regimens are the current first-line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine-induced killer (CIK) cell immunotherapy and first-line chemotherapy in patients with mCRC.

Methods: This retrospective study included 252 patients with mCRC treated with first-line chemotherapy.

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery.

miR-183-5p regulates uterine receptivity and enhances embryo implantation.

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood.

PD-L1 expression patterns in tumour cells and their association with CD8 tumour infiltrating lymphocytes in clear cell renal cell carcinoma.

: To evaluate the tumour cell PD-L1 (TC-PD-L1) expression patterns in the local microenvironment of clear cell renal cell carcinoma (ccRCC). : 30 fresh primary ccRCC tissues were used to detect the association between TC-PD-L1 and CD8TILs at mRNA level. The incubation experiment was used to confirm the association between extrinsic TC-PD-L1 expression and IFNγ.

Safety and activity of PD-1 blockade-activated DC-CIK cells in patients with advanced solid tumors.

Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors.

PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma.

Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients.

Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: implications for prognosis.

To examine the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) expression and esophageal carcinoma prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded primary tumor specimens from 158 patients with esophageal cancer. CTLA-4 was detected in the cytoplasm and cell membranes of esophageal cancer cells and in interstitial lymphocytes. In univariate analyses (log-rank), higher interstitial CTLA-4+ lymphocyte density and higher tumor CTLA-4 expression were associated with shorter overall survival (OS).

Bromodomain-containing protein 7 (BRD7) as a potential tumor suppressor in hepatocellular carcinoma.

Bromodomain-containing protein 7 (BRD7) is a subunit of the PBAF complex, which functions as a transcriptional cofactor for the tumor suppressor protein p53. Down-regulation of BRD7 has been demonstrated in multiple types of cancer. This study aimed to investigate BRD7 expression and its tumor suppressive effect in hepatocellular carcinoma (HCC).

A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma.

This report describes an ongoing Phase I clinical trial testing the safety of adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) in patients with primary hepatocellular carcinoma (HCC). Fifteen HCC patients were treated with their activated and expanded TILs following tumor resection. From a total of 17 patients with HCC, TIL were successfully expanded from 15 patients (88%), whereas two patients showed minimal or no expansion of TIL.

Overexpression of WWP1 promotes tumorigenesis and predicts unfavorable prognosis in patients with hepatocellular carcinoma.

WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been speculated to play important roles in the development of several kinds of cancers. However, the role of WWP1 in hepatocellular carcinoma(HCC) is not clear. In the present study, we investigated the expression and prognostic role of WWP1 in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples.

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer.

Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells.

A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Chinese family with familial adenomatous coli.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease manifesting as colorectal cancer in middle-aged patients. Mutations of the adenomatous polyposis coli (APC) gene contribute to both FAP and sporadic or familial colorectal carcinogenesis. Here we describe the identification of the causative APC gene defects associated with FAP in a Chinese pedigree.

A nomogram for predicting the benefit of adjuvant cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma.

The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed a prognostic nomogram to enable individualized predictions of survival benefit of adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) for patients in the hepatectomy/CIK combination group were 41 and 16 months, respectively, compared to 28 and 12 months for patients in the hepatectomy alone group (control).

Expression and prognostic role of ubiquitination factor E4B in primary hepatocellular carcinoma.

Ubiquitination factor E4B (UBE4B) has been speculated to have contradictory functions upon tumorigenesis as an oncogene or tumor suppressor in different types of cancers. We investigated the expression and prognostic role of UBE4B in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of UBE4B in HCC was also explored.

Annexin A3 as a potential target for immunotherapy of liver cancer stem-like cells.

Cancer stem-like cells/cancer-initiating cells (CSCs/CICs) are considered to represent a small population of cancer cells that is resistant to conventional cancer treatments and responsible for tumor recurrence and metastasis. The aim of this study was to establish CSC/CIC-targeting immunotherapy. In this study, we found that Annexin A3 (ANXA3) was preferentially expressed in CSCs/CICs derived from hepatocellular carcinoma (HCC) cells compared to non-CSCs/CICs.

Galectin-3 is associated with a poor prognosis in primary hepatocellular carcinoma.

Background: Galectin-3, a member of the beta-galactoside-binding lectin family, is a multifunctional protein with various biological functions, including the proliferation and differentiation of tumor cells, angiogenesis, cancer progression, and metastasis. We aimed to clarify if expression of galectin-3 is related to the clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC) patients, and to explore the possible mechanisms of galectin-3 in hepatocellular carcinoma.

Methods: First, we investigated galectin-3 mRNA and protein expression by using RT-PCR and Western blotting.

Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma: role for CD57+ NK cells.

The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues, and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS).

Reduced expression of uroplakin 1A is associated with the poor prognosis of gastric adenocarcinoma patients.

Background: The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.

Methodology/principal Findings: Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples.

Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in patients with post-mastectomy triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) is a high risk form of this disease, even after surgery, due to the absence of targets for hormone treatment and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such patients with breast cancer, although the outcome is often unsatisfactory. Thus, the development of combination adjuvant therapies is essential for improved prognosis in patients with TNBC.

Decreased expression of the FOXO3a gene is associated with poor prognosis in primary gastric adenocarcinoma patients.

Background: FOXO3a, a member of the forkhead class 'O' (FOXO) transcription factor family, controls a wide spectrum of biological processes, such as DNA damage repair, apoptosis, and cell cycle regulation. FOXO3a has been shown to be a tumor suppressor in various cancers. This study investigated the expression of FOXO3a in primary gastric adenocarcinomas and its prognostic value for primary gastric adenocarcinoma patients.