Tumor Cell-Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079701" target="_blank" >RIV/00159816:_____/23:00079701 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/23:00131664

Výsledek na webu

<a href="https://aacrjournals.org/cancerimmunolres/article/11/10/1432/729299/Tumor-Cell-Intrinsic-c-Myb-Upregulation-Stimulates" target="_blank" >https://aacrjournals.org/cancerimmunolres/article/11/10/1432/729299/Tumor-Cell-Intrinsic-c-Myb-Upregulation-Stimulates</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/2326-6066.CIR-22-0912" target="_blank" >10.1158/2326-6066.CIR-22-0912</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Tumor Cell-Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model

Popis výsledku v původním jazyce

The authors show c-Myb in tumor cells induces expression of immune-related genes, resulting in immunomodulation and tumor growth inhibition. The findings provide a possible mechanistic explanation for the observed better prognosis in cancer patients with higher c-Myb expression. The transcription factor c-Myb is overexpressed in many different types of solid tumors, including colorectal cancer. However, its exact role in tumorigenesis is unclear. In this study, we show that tumor-intrinsic c-Myb expression in mouse models of colon cancer and melanoma suppresses tumor growth. Although no differences in proliferation, apoptosis, and angiogenesis of tumors were evident in tumors with distinct levels of c-Myb expression, we observed changes in intratumoral immune cell infiltrates. MC38 tumors with upregulated c-Myb expression showed increased numbers of CD103+ dendritic cells and eosinophils, but decreased tumor-associated macrophages (TAM). Concomitantly, an increase in the number of activated cytotoxic CD8+ T cells upon c-Myb upregulation was observed, which correlated with a pro-inflammatory tumor microenvironment and increased numbers of M1 polarized TAMs. Mechanistically, c-Myb upregulation in immunogenic MC38 colon cancer cells resulted in enhanced expression of immunomodulatory genes, including those encoding beta 2-microglobulin and IFN beta, and decreased expression of the gene encoding the chemokine receptor CCR2. The increased numbers of activated cytotoxic CD8+ T cells contributed to tumor growth attenuation. In poorly immunogenic CT26, LLC, and B16-BL6 tumor cells, c-Myb upregulation did not affect the immunomodulatory gene expression. Despite this, c-Myb upregulation led to reduced B16-BL6 tumor growth but it did not affect tumor growth of CT26 and LLC tumors. Altogether, we postulate that c-Myb functions as a tumor suppressor in a tumor cell-type specific manner and modulates antitumor immunity.

Název v anglickém jazyce

Tumor Cell-Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model

Popis výsledku anglicky

The authors show c-Myb in tumor cells induces expression of immune-related genes, resulting in immunomodulation and tumor growth inhibition. The findings provide a possible mechanistic explanation for the observed better prognosis in cancer patients with higher c-Myb expression. The transcription factor c-Myb is overexpressed in many different types of solid tumors, including colorectal cancer. However, its exact role in tumorigenesis is unclear. In this study, we show that tumor-intrinsic c-Myb expression in mouse models of colon cancer and melanoma suppresses tumor growth. Although no differences in proliferation, apoptosis, and angiogenesis of tumors were evident in tumors with distinct levels of c-Myb expression, we observed changes in intratumoral immune cell infiltrates. MC38 tumors with upregulated c-Myb expression showed increased numbers of CD103+ dendritic cells and eosinophils, but decreased tumor-associated macrophages (TAM). Concomitantly, an increase in the number of activated cytotoxic CD8+ T cells upon c-Myb upregulation was observed, which correlated with a pro-inflammatory tumor microenvironment and increased numbers of M1 polarized TAMs. Mechanistically, c-Myb upregulation in immunogenic MC38 colon cancer cells resulted in enhanced expression of immunomodulatory genes, including those encoding beta 2-microglobulin and IFN beta, and decreased expression of the gene encoding the chemokine receptor CCR2. The increased numbers of activated cytotoxic CD8+ T cells contributed to tumor growth attenuation. In poorly immunogenic CT26, LLC, and B16-BL6 tumor cells, c-Myb upregulation did not affect the immunomodulatory gene expression. Despite this, c-Myb upregulation led to reduced B16-BL6 tumor growth but it did not affect tumor growth of CT26 and LLC tumors. Altogether, we postulate that c-Myb functions as a tumor suppressor in a tumor cell-type specific manner and modulates antitumor immunity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer Immunology Research

ISSN

2326-6066

e-ISSN

2326-6074

Svazek periodika

11

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

1432-1444

Kód UT WoS článku

001083129700012

EID výsledku v databázi Scopus

—