Nucleic acid-triggered tumoral immunity propagates pH-selective therapeutic antibodies through tumor-driven epitope spreading.

Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs).

Postprandial Asymptomatic Glycemic Fluctuations after Gastrectomy for Gastric Cancer Using Continuous Glucose Monitoring Device.

Purpose: Although dumping symptoms are thought to involve postprandial glycemic changes, postprandial glycemic variability without dumping symptoms remains poorly understood due to the lack of a method that allows the easy and continuous measurement of blood glucose levels.

Materials And Methods: Patients having undergone distal gastrectomy with Billroth-I (DG-BI) or Roux-en-Y reconstruction (DG-RY), total gastrectomy with RY (TG-RY) and pylorus preserving gastrectomy (PPG) for gastric cancer 3 months to 3 years prior, diagnosed as pathological stage I or II, were prospectively enrolled from March 2018 to January 2020. The interstitial tissue glycemic levels were measured every 15 min, up to 14 days by continuous glucose monitoring.

Is proximal gastrectomy indicated for locally advanced cancer in the upper third of the stomach?

Aim: To treat upper third gastric cancer, proximal gastrectomy (PG), a function-preserving procedure, is recommended for early lesions when at least half the distal stomach can be preserved, while total gastrectomy (TG) is standard for locally advanced lesions. Oncological feasibility, when applying PG for such lesions, remains unknown.

Methods: We reviewed patients undergoing TG for clinical (c) T2-T4 upper third gastric cancer between 2006 and 2015.

Preliminary prospective study of real-time post-gastrectomy glycemic fluctuations during dumping symptoms using continuous glucose monitoring.

Background: Although dumping symptoms constitute the most common post-gastrectomy syndromes impairing patient quality of life, the causes, including blood sugar fluctuations, are difficult to elucidate due to limitations in examining dumping symptoms as they occur.

Aim: To investigate relationships between glucose fluctuations and the occurrence of dumping symptoms in patients undergoing gastrectomy for gastric cancer.

Methods: Patients receiving distal gastrectomy with Billroth-I (DG-BI) or Roux-en-Y reconstruction (DG-RY) and total gastrectomy with RY (TG-RY) for gastric cancer (March 2018-January 2020) were prospectively enrolled.

Favorable Outcomes of Neoadjuvant Chemotherapy and Limited Para-Aortic Lymph Node Dissection for Advanced Gastric Cancer with Para-aortic Lymph Node Metastasis.

Background: Although para-aortic lymph node (PALN) metastasis from gastric cancer is a non-curative lesion, gastrectomy with complete PALN dissection (PAND) following neoadjuvant chemotherapy (NAC) is a tentative standard treatment in Japan, based on the results of a small-scale phase II clinical trial. However, whether complete PAND (C-PAND) is always necessary for such diseases is open to debate.

Methods: Patients who received NAC followed by R0 gastrectomy for gastric cancer with clinical PALN metastasis at the Cancer Institute Hospital in Tokyo from 2005 to 2017 were reviewed in the present study.

Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases.

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex.

Capturing the differences between humoral immunity in the normal and tumor environments from repertoire-seq of B-cell receptors using supervised machine learning.

Background: The recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments.