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

J 2023

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

VAN GOGH, Merel; Jesus F. Glaus GARZON; Dilara SAHIN; Lucia KNOPFOVÁ; Petr BENEŠ et al.

Základní údaje

Originální název

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

Autoři

VAN GOGH, Merel; Jesus F. Glaus GARZON; Dilara SAHIN; Lucia KNOPFOVÁ; Petr BENEŠ; Onur BOYMAN; Igor JURISICA a Lubor BORSIG

Vydání

Cancer Immunology Research, American Association for Cancer Research, 2023, 2326-6066

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.100

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00131664

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

c-Myb; colorectal cancer; antitumor immunity

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 2. 2024 08:11, prof. Mgr. Petr Beneš, Ph.D.

Anotace

V originále

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 β2-microglobulin and IFNβ, 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.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

Přiložené soubory

2309978.pdf

Citovat

VAN GOGH, Merel; Jesus F. Glaus GARZON; Dilara SAHIN; Lucia KNOPFOVÁ; Petr BENEŠ; Onur BOYMAN; Igor JURISICA a Lubor BORSIG. Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model. Cancer Immunology Research. American Association for Cancer Research, 2023, roč. 11, č. 10, s. 1432-1444. ISSN 2326-6066. Dostupné z: https://doi.org/10.1158/2326-6066.CIR-22-0912.

@article{2309978,
   author = {van Gogh, Merel and Garzon, Jesus F. Glaus and Sahin, Dilara and Knopfová, Lucia and Beneš, Petr and Boyman, Onur and Jurisica, Igor and Borsig, Lubor},
   article_number = {10},
   doi = {https://doi.org/10.1158/2326-6066.CIR-22-0912},
   keywords = {c-Myb; colorectal cancer; antitumor immunity},
   language = {eng},
   issn = {2326-6066},
   journal = {Cancer Immunology Research},
   title = {Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model},
   url = {https://doi.org/10.1158/2326-6066.CIR-22-0912},
   volume = {11},
   year = {2023}
}

TY  - JOUR
ID  - 2309978
AU  - van Gogh, Merel - Garzon, Jesus F. Glaus - Sahin, Dilara - Knopfová, Lucia - Beneš, Petr - Boyman, Onur - Jurisica, Igor - Borsig, Lubor
PY  - 2023
TI  - Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model
JF  - Cancer Immunology Research
VL  - 11
IS  - 10
SP  - 1432-1444
EP  - 1432-1444
PB  - American Association for Cancer Research
SN  - 23266066
KW  - c-Myb
KW  - colorectal cancer
KW  - antitumor immunity
UR  - https://doi.org/10.1158/2326-6066.CIR-22-0912
N2  - 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 β2-microglobulin and IFNβ, 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.
ER  -

VAN GOGH, Merel; Jesus F. Glaus GARZON; Dilara SAHIN; Lucia KNOPFOVÁ; Petr BENEŠ; Onur BOYMAN; Igor JURISICA a Lubor BORSIG. Tumor Cell–Intrinsic c-Myb Upregulation Stimulates Antitumor Immunity in a Murine Colorectal Cancer Model. \textit{Cancer Immunology Research}. American Association for Cancer Research, 2023, roč.~11, č.~10, s.~1432-1444. ISSN~2326-6066. Dostupné z: https://doi.org/10.1158/2326-6066.CIR-22-0912.

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