Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier.

To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles).

Tumor-infiltrating Tim-3 T cells proliferate avidly except when PD-1 is co-expressed: Evidence for intracellular cross talk.

Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3.

High expression of CD11c indicates favorable prognosis in patients with gastric cancer.

Aim: To determine the relationship between CD11c expression level and prognosis in patients with gastric cancer (GC).

Methods: This retrospective survival study was performed from July 31, 2008 to June 30, 2014. Our study inclusion criteria included all the patients with GC who underwent surgical resection between January 1998 and December 2009 in the Third Affiliated Hospital of Soochow University.

Mechanism of T cell regulation by microRNAs.

MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that can modulate target gene expression at post-transcriptional level and participate in cell proliferation, differentiation, and apoptosis. T cells have important functions in acquired immune response; miRNAs regulate this immune response by targeting the mRNAs of genes involved in T cell development, proliferation, differentiation, and function. For instance, miR-181 family members function in progression by targeting Bcl2 and CD69, among others.

Expression of costimulatory molecule B7-H4 in human malignant tumors.

Costimulatory molecule B7-H4, a member of the B7 family, negatively regulates the immune response of T cells through inhibiting their proliferation, cytokine production and cell cycle. The overexpression of B7-H4 plays an important role in initiation, progression and regression of tumors by promoting malignant transformation of epithelial cells and protecting epithelial cells from anoikis. B7-H4 expression in malignant tumors is useful for clinical diagnosis, and may provide a novel molecular target for cancer treatment.

Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer.

In the present study, we studied the expression of T-bet, a key marker for type 1 immune responses, within the tumor microenvironment of gastric cancer, and analyzed its association with clinicopathological parameters. One hundred and fifty-two archival paraffin-embedded gastric tumor tissues were collected, and the expression of T-bet in these cancer tissue specimens was examined by immunohistochemistry. T-bet(+) tumor-infiltrating lymphocytes (TILs) in some gastric cancer tissues were further characterized by flow cytometric analysis.

B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma.

A retrospective cohort study including 112 patients suffering from esophageal squamous cell carcinoma (ESCC) was performed to investigate the expression of B7-H4 in ESCC and determine its association with patient's clinicopathological parameters and survival. Expression levels of B7-H4 on tumor cells and densities of tumor infiltrating lymphocytes (TILs) in the surgical specimens of ESCC tissues were characterized using immunohistochemical assays. Uni- and multivariate analyses were performed to evaluate the prognostic value of B7-H4 expression levels and densities of TILs in tumor sections.

Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients.

Aim: to analyze the correlation between cytokine-induced killer (cik) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. methods: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire.

[Influence of co-stimulatory molecules B7-H4 expression on the prognosis of patients with gastric cancer treated with cytokine-induced killer cells adoptive immunotherapy].

Objective: To investigate the influence of co-stimulatory molecules B7-H4 expression on prognosis of gastric cancer patients treated by cytokine-induced killer cells (CIK cells) adoptive immunotherapy.

Methods: Clinical data of 156 cases of gastric cancer patients were retrospectively analyzed. Patients were divided into chemotherapy group(n=81) and chemotherapy combined with CIK cell therapy group(n=75).

Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma.

B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses, and was shown to either promote or inhibit T-cell responses in various experimental systems. B7-H3 was expressed in some human cancers and correlated with poor outcome of cancer patients. However, its exact role in cancer is not known.