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Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [CITE-seq]

ABSTRACT: Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [CITE-seq]

PROVIDER: PRJNA1024490 | ENA |

REPOSITORIES: ENA

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Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer

Project description:Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer

| PRJNA1024484 | ENA

Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [CITE-seq]

Project description:Sotigalimab (sotiga) is an agonistic anti-CD40 monoclonal antibody that can modulate anti-tumor immune responses. In a clinical trial of sotiga combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction cancer, treatment induced pathologic complete responses in 38% of patients. Using high-dimensional single cell techniques, we found that sotiga dramatically re-modeled both peripheral immune responses and the tumor microenvironment (TME), increasing components of antigen processing and presentation and altering metabolic pathways in myeloid cells. Concomitant with myeloid cell alterations, sotiga primed new T cell clonotypes, increased T cells with enhanced cytotoxic activity, and decreased the frequency of Tregs in the TME. Clinical responses were associated with both baseline and treatment-induced T cell states. These findings indicate that sotiga induces antigen presentation leading to enhanced T cell activation and clinical response, and that the immune composition of the TME at baseline is important in conferring sensitivity to this treatment approach.

2023-12-11 | GSE244746 | GEO

Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [scRNA-seq]

2023-12-11 | GSE244739 | GEO

Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [scRNA-seq]

Project description:Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer [scRNA-seq]

| PRJNA1024473 | ENA

Neoadjuvant CD40 Agonism Remodels the Tumor Immune Microenvironment in Locally Advanced Esophageal/Gastroesophageal Junction Cancer.

Project description:Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer with the primary outcome of efficacy as measured by pathologic complete response (pCR) rate, the combination induced pCR in 38% of treated patients. We investigated the mechanism of action of sotigalimab in samples obtained from this clinical trial. Tumor biopsies and peripheral blood samples were collected at baseline, following an initial dose of sotigalimab, and at the time of surgery after CRT completion from six patients. High dimensional single-cell techniques were used, including combined single-cell RNA-sequencing and proteomics (CITEseq) and multiplexed ion beam imaging, to analyze immune responses. Sotigalimab dramatically remodeled the immune compartment in the periphery and within the tumor microenvironment (TME), increasing expression of molecules related to antigen processing and presentation and altering metabolic pathways in myeloid cells. Concomitant with these changes in myeloid cells, sotigalimab treatment primed new T cell clonotypes and increased the density and activation of T cells with enhanced cytotoxic function. Sotigalimab treatment also induced a decrease in the frequency of Tregs in the TME. These findings indicate that a single dose of sotigalimab leads to enhanced antigen presentation that can activate T cells and induce new T cell clones. This restructuring of the TME provides elements which are critical to the development of effective antitumor immune responses and improved clinical outcomes.

| S-EPMC10809910 | biostudies-literature

Neoadjuvant CD40 agonism remodels the tumor immune microenvironment in locally advanced esophageal/gastroesophageal junction cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-10 | GSE244748 | GEO

Genomic profiling of gastroesophageal adenocarcinoma

Project description:We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas using 32k high-resolution array-based comparative genomic hybridization (aCGH) and 27k oligo gene expression arrays and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-q23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike. Three types of gastroesophageal adenocarcinomas; 7 distal esophageal (EA) tumors, 9 junctional (JA) and 7 proximal stomach cancers (GA) was genomically profiled using tiling 32k BAC-arrays. Two replicates of tumors IDs 1-EA-CGH (replicate 1-EA-CGH-2), 12-EA-CGH (replicate 12-EA-CGH-2) and 18-EA-CGH (replicate 18-EA-CGH-2). Reference samples consist of a pool of male DNA (Promega, Madison, WI, USA).

2010-06-24 | E-GEOD-22524 | biostudies-arrayexpress

Locally advanced gastroesophageal junction tumor: a treatment dilemma.

Project description:Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research.

| S-EPMC4319638 | biostudies-other

A Phase II Trial of Adjuvant Durvalumab following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study

Project description:Correlative analysis using RNA-seq was performed on tumor samples from patients with locally advanced esophageal and gastroesophageal junction adenocarcinoma treated with adjuvant durvalumab as part of a Phase II trial. The primary goal of this correlative analysis was to perform immune deconvolution using CIBERSORTx in order to determine the relative proportion of immune cell types in each sample. The immune components were then associated with relapse free survival.

2021-09-12 | GSE183924 | GEO

Gene expression profiling of gastroesophageal adenocarcinoma

Project description:We aimed to genetically characterize adenocarcinomas in the gastroesophagel junction in relation to cancers in the esophagus and the stomach. In total 27 tumors was genetically profiled using gene expression array. Adenocarcinomas located in the gastroesophageal junction showed strong similarites with tumors in the distal esophagus, whereas different profiles were generated for tumors in the proximal stomach. Three types of gastroesophageal adenocarcinomas; 10 distal esophageal (EA) tumors, 9 junctional (JA) and 8 proximal stomach cancers (GA) was undergone differentially analysis based on gene expression profiles. One replicate of tumor ID 27_JA (replicate ID 27_JA_2) and one replicate of tumor ID 3-GA (replicate ID 3-GA-2). Reference samples consist of the Stratagene Universal Reference (10 cellines), commercially obtained from Stratagene, La Jolla, CA, USA.

2010-05-29 | E-GEOD-22050 | biostudies-arrayexpress

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