Molecularly resolved mapping of heterogeneous ice nucleation and crystallization pathways using in-situ cryo-TEM.

Crystallization plays a fundamental role in diverse fields such as glaciology, geology, biology, and materials science. Among various crystallizing systems, the formation of ice remains elusive, despite decades of intensive investigation. In this study, we integrate in-situ cryogenic transmission electron microscopy with molecular dynamics simulations to develop a molecular-resolution mapping and thermodynamic framework for deposition freezing under low-temperature, low-pressure conditions.

Impact of Tregs on tumor regression in locally advanced G/GEJ cancer patients undergoing neoadjuvant chemoimmunotherapy.

Neoadjuvant chemoimmunotherapy has transformed the treatment of locally advanced gastric or gastroesophageal junction (G/GEJ) cancer. However, identifying reliable predictive markers for treatment efficacy remains challenging. We conducted a retrospective analysis to evaluate the prognostic value of peripheral blood regulatory T (Treg) cells in patients with G/GEJ cancer undergoing neoadjuvant chemoimmunotherapy followed by curative resection.

The baseline circulating immunophenotype characteristics associate with PD(L)-1 targeted treatment response, irae onset, and prognosis.

More promising, effective, and less-invasive biomarkers for PD(L)-1 targeted responses, immune-related adverse events (irAEs), and prognosis are being explored. We conducted a single-center retrospective study in pan-cancer patients with anti-PD(L)-1 monotherapy. Observational endpoints included treatment response, prognosis, and irAEs.

Utility of the neutrophil-to-lymphocyte ratio and the ratio of neutrophil-to-lymphocyte ratio after and before adverse events for differential diagnosis of immune-related adverse events and bacterial infections in cancer patients treated with PD-(L)1 inhibitors.

Differential diagnosis of immune-related adverse events (irAEs) or bacterial infections is sometimes very difficult in cancer patients undergoing treatment with PD-(L)1 inhibitors. This study aimed to assess the effectiveness of the neutrophil-to-lymphocyte ratio (NLR) in distinguishing between irAEs and bacterial infections in cancer patients receiving PD-(L)1 inhibitors. We conducted a retrospective analysis of cancer patients who received at least 1 dose of PD-(L)1 inhibitors at Affiliated Cancer Hospital of Zhengzhou University from 2018 to 2023.

Antiviral therapy can effectively suppress irAEs in HBV positive hepatocellular carcinoma treated with ICIs: validation based on multi machine learning.

Background: Immune checkpoint inhibitors have proven efficacy against hepatitis B-virus positive hepatocellular. However, Immunotherapy-related adverse reactions are still a major challenge faced by tumor immunotherapy, so it is urgent to establish new methods to effectively predict immunotherapy-related adverse reactions.

Objective: Multi-machine learning model were constructed to screen the risk factors for irAEs in ICIs for the treatment of HBV-related hepatocellular and build a prediction model for the occurrence of clinical IRAEs.

Combination therapy using low-dose anlotinib and immune checkpoint inhibitors for extensive-stage small cell lung cancer.

Background: This study evaluated the efficacy and safety of low-dose anlotinib combined with immune checkpoint inhibitors as second-line or later treatment for extensive-stage small cell lung cancer (ES-SCLC).

Methods: The study included 42 patients with ES-SCLC who were treated with low-dose anlotinib combined with programmed cell death protein 1/programmed cell death-ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022. We retrospectively analyzed the efficacy and safety data for these patients.

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle.

CD69 Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC), one of the malignancies with a wide expression of stress ligands recognized by Vδ1γδ T cells, has received much attention in adoptive immunotherapy of γδ T cells. In this study, we aimed to identify the potential anti-tumor Vδ1γδ T subpopulations in HCC.

Methods: Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University.

Modes of Nanodroplet Formation and Growth on an Ultrathin Water Film.

Using nanobubbles as geometrical confinements, we create a thin water film (∼10 nm) in a graphene liquid cell and investigate the evolution of its instability at the nanoscale under transmission electron microscopy. The breakdown of the water films, resulting in the subsequent formation and growth of nanodroplets, is visualized and generalized into different modes. We identified distinct droplet formation and growth modes by analyzing the dynamic processes involving 61 droplets and 110 liquid bridges within 31 Graphene Liquid Cells (GLCs).

An EBV-related CD4 TCR immunotherapy inhibits tumor growth in an HLA-DP5+ nasopharyngeal cancer mouse model.

Adoptive transfer of T cell receptor-engineered T cells (TCR-T) is a promising strategy for immunotherapy against solid tumors. However, the potential of CD4+ T cells in mediating tumor regression has been neglected. Nasopharyngeal cancer is consistently associated with EBV.

Cytokine-induced killer (CIK) cells, successes and challenges: report on the first international conference dedicated to the clinical translation of this unique adoptive cell immunotherapy.

On August 30, 2023, experts from Germany and abroad met to discuss the successes and challenges of cytokine-induced killer cell (CIK) therapy, that recently celebrated its 30th anniversary providing treatment for cancer. This first virtual conference was hosted by CIO Bonn, a certified Comprehensive Cancer Center (CCC) funded by German Cancer Aid (DKH). In addition to keynote speakers involved in CIK cell clinical trials or optimized preclinical models to improve this adoptive cell immunotherapy, more than 100 attendees from around the world also participated in this event.

The inter-link of ageing, cancer and immunity: findings from real-world retrospective study.

Background: Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce.

Methods: In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes.

Adjusting the dose of traditional drugs combined with immunotherapy: reshaping the immune microenvironment in lung cancer.

Immunotherapy is currently the most promising clinical treatment for lung cancer, not only revolutionizing second-line therapy but now also approved for first-line treatment. However, its clinical efficiency is not high and not all patients benefit from it. Thus, finding the best combination strategy to expand anti-PD-1/PD-L1-based immunotherapy is now a hot research topic.

In vivo growth of subclones derived from Lewis lung carcinoma is determined by the tumor microenvironment.

Heterogeneity is a fundamental feature of human tumors and plays a major role in drug resistance and disease progression. In the present study, we selected single-cell-derived cell lines (SCDCLs) derived from Lewis lung carcinoma (LLC1) cells to investigate tumorigenesis and heterogeneity. SCDCLs were generated using limiting dilution.

A two-pronged strategy to alleviate tumor hypoxia and potentiate photodynamic therapy by mild hyperthermia.

The application of photodynamic therapy (PDT) is limited by tumor hypoxia. To overcome hypoxia, catalase-like nanozymes are often used to catalyze endogenous HO enriched in tumor tissues to O. Nonetheless, the catalase activity may not be optimal at body temperature and the O supply may not meet the rapid O consumption of PDT.

Identification of novel HLA-A*11:01-restricted HPV16 E6/E7 epitopes and T-cell receptors for HPV-related cancer immunotherapy.

Background: E6 and E7 oncoproteins are considered ideal antigens of T cell therapy for human papillomavirus (HPV)-related cancers. However, little is known about the epitopes of E6 and E7 presented by HLA-A*11:01, one of the most prevalent HLA types globally, especially in Asia.

Methods: We combined and experimental approaches to identify endogenously processed HLA-A*11:01-restricted epitopes of HPV16 E6 and E7.

Sintilimab maintenance therapy post first-line cytokine-induced killer cells plus chemotherapy for extensive-stage small cell lung cancer.

Unlabelled: Despite recent progress in treating advanced non-small cell lung cancer, clinical intervention in extensive-stage small-cell lung cancer (ES-SCLC) remains stagnant. The purpose of this study was to evaluate the clinical efficacy of cytokine-induced killer (CIK) cells combined with cytotoxic chemotherapy, followed by anti-programmed death 1 antibody (sintilimab) maintenance, in ES-SCLC patients. To explore a new method for safe treatment of ES-SCLC patients, thirteen ES-SCLC patients were enrolled between June 2019 and December 2021.

Low-dose anlotinib confers improved survival in combination with immune checkpoint inhibitor in advanced non-small cell lung cancer patients.

Background: Anti-angiogenic drugs increase anti-tumor efficacy of immune checkpoint inhibitors (ICIs). However, the optimal dose of anti-angiogenic drugs remains unclear.

Methods: We retrospectively analyzed efficacy and safety data from patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) that received PD-1 blockade with low-doses of anlotinib, a highly selective receptor tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptors, as second or later line therapy.

Combination of Low-Dose Gemcitabine and PD-1 Inhibitors for Treatment in Patients With Advanced Malignancies.

Purpose: This study determined the efficacy of low-dose gemcitabine combined with programmed death-1 (PD-1) inhibitors for treating multiple malignancies, providing a cost-effective and safe treatment option.

Study Design: This study included 61 patients with advanced solid tumors treated with low-dose gemcitabine combined with PD-1 inhibitors at the Henan Cancer Hospital between January 2018 and February 2022. We retrospectively reviewed medical records to evaluate several clinical factors, including progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and objective response to treatment.

Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy.

Background: High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy.

Methods: This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020.

Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma.

Background: The prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study's objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma.

Methods: This was a single-arm, single-center phase II trial.

Identification of an immune gene-associated prognostic signature in patients with bladder cancer.

A deeper understanding of the interaction between tumor cell and the immune microenvironment in bladder cancer may help select predictive and prognostic biomarkers. The current study aims to construct a prognostic signature for bladder cancer by analysis of molecular characteristics, as well as tumor-immune interactions. RNA-sequencing and clinical information from bladder cancer patients were downloaded from the TCGA database.