Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer DOI
Heather M. McGee,

Joseph D. Bonner,

Colt A. Egelston

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and etiology disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental as-yet unidentified contributors their interactions. Previous research linked variation on chromosome 6 increased risk. This region harbors multiple immune genes, including gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand Natural Killer Group 2D receptor (NKG2D), expressed (NK) cells other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable outcomes, we hypothesized germline in

Язык: Английский

Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer DOI Creative Commons
Qian Chen,

Dongfeng Deng,

Hong Zhu

и другие.

World Journal of Surgical Oncology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 14, 2025

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC LOCC samples to compare immune architectures. Epithelial cells in exhibited a notable dual phenotype, characterized immune-suppressive properties driven elevated CXCL production, alongside immune-stimulatory features linked heightened HLA molecule expression. CD4 + CD8 T demonstrated activation state, while NK diminished cytotoxicity. Macrophages displayed enhanced polarization towards both M1 M2 phenotypes, along with dendritic showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), was enriched inflammatory CAFs, whereas harbored higher proportion of CAFs. These findings reveal the multifaceted heterogeneity between LOCC, underscoring imperative for age-tailored immunotherapeutic strategies.

Язык: Английский

Процитировано

0

The Current Status of T Cell Receptor (TCR) Repertoire Analysis in Colorectal Cancer DOI Open Access

Hiroyuki Takahashi,

Katsuzo Hanaoka,

Hideo Wada

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2698 - 2698

Опубликована: Март 17, 2025

The rapid increase in colorectal cancer (CRC) cases recently has highlighted the need to use predictive biomarkers guide therapeutic approaches. Current studies have focused on tumor-infiltrating lymphocytes present tumor microenvironment (TME), which cytotoxic T cell activation and amount are associated with CRC patient prognosis. receptor (TCR) is essential for antigen recognition identification, playing a central role immunotherapy. status reflects TCR diversity or clonality, known as repertoire. Accordingly, analyzing repertoire dynamics may help predict immunological circumstances of TME timely way. In this review, we summarize repertoire-related knowledge, including its potential CRC. intratumoral restricted patients compared healthy individuals, well peripheral blood. Patients deficient mismatch repair display more restriction than those proficient repair. Importantly, higher before treatment decrease following indicate good response better clinical outcome patients. future sequencing technology combined artificial intelligence-based analysis strategy decision making.

Язык: Английский

Процитировано

0

Colorectal Organoids: Models, Imaging, Omics, Therapy, Immunology, and Ethics DOI Creative Commons
Martina Taglieri,

Linda Di Gregorio,

Serena Matis

и другие.

Cells, Год журнала: 2025, Номер 14(6), С. 457 - 457

Опубликована: Март 19, 2025

Colorectal epithelium was the first long-term 3D organoid culture established in vitro. Identification of key components essential for survival stem cell niche allowed an indefinite propagation these cultures and modulation their differentiation into various lineages mature intestinal epithelial cells. While methods were eventually adapted to establish organoids from different organs, colorectal remain a pioneering model development new applications health disease. Several basic applicative aspects culture, modeling, monitoring testing are analyzed this review. We also tackle ethical problems biobanking distribution precious research tools, frequently confined laboratory origin or condemned destruction at end project.

Язык: Английский

Процитировано

0

Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer DOI Creative Commons
Jianhui Zhao,

Haosen Ji,

Kangning Li

и другие.

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 18, 2025

Abstract Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this remain unclear. The etiology of EOCRC is complex could involve both genetic environmental factors. Apart from Lynch syndrome Familial Adenomatous Polyposis, sporadic exhibits broad spectrum pathogenic germline mutations, polymorphisms, methylation changes, chromosomal instability. Early-life exposures risk factors, including lifestyle dietary have been found be associated risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, metabolic syndrome, EOCRC. Interactions between factors also explored. Here we present findings narrative review studies on assessment early-life exposures, EOCRC-specific their interactions susceptible loci. We results genome-wide association that used perform Mendelian randomization analyses ascertain potential causal links

Язык: Английский

Процитировано

0

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer DOI
Heather M. McGee,

Joseph D. Bonner,

Colt A. Egelston

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and etiology disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental as-yet unidentified contributors their interactions. Previous research linked variation on chromosome 6 increased risk. This region harbors multiple immune genes, including gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand Natural Killer Group 2D receptor (NKG2D), expressed (NK) cells other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable outcomes, we hypothesized germline in

Язык: Английский

Процитировано

0