Establishment and characterization of a mouse tumor cell line with irreversible downregulation of MHC class I molecules

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10404119" target="_blank" >RIV/00216208:11310/19:10404119 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3XMmLHE-Jy" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3XMmLHE-Jy</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/or.2019.7356" target="_blank" >10.3892/or.2019.7356</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Establishment and characterization of a mouse tumor cell line with irreversible downregulation of MHC class I molecules

Popis výsledku v původním jazyce

In the majority of human tumors, downregulation of major histocompatibility complex class I (MHC-I) expression contributes to the escape from the host immune system and resistance to immunotherapy. Relevant animal models are therefore needed to enhance the efficacy of cancer immunotherapy. As loss of beta-2 microglobulin expression results in irreversible downregulation of surface MHC-I molecules in various human tumors, the beta-2 microglobulin gene (B2m) was deactivated in a mouse oncogenic TC-1 cell line and a TC-1/dB2m cell line that was negative for surface MHC-I expression was derived. Following stimulation with interferon gamma, MHC-I heavy chains, particularly the H-2D(b) molecules, were found to be expressed at low levels on the cell surface, but without beta-2 microglobulin. B2m deactivation in TC-1/dB2m cells led to reduced proliferation and tumor growth. These cells were insensitive to DNA vaccination and only weakly responsive to combined immunotherapy with a DNA vaccine and the ODN1826 adjuvant. In vivo depletion demonstrated that NK1.1(+) cells were involved in both reduced tumor growth and an antitumor effect of immunotherapy. The number of immune cells infiltrating TC-1/dB2m-induced tumors was comparable with that in tumors developing from TC-1/A9 cells characterized by reversible MHC-I downregulation. However, the composition of the cell infiltrate was different and, most importantly, infiltration with immune cells was not increased in TC-1/dB2m tumors after immunotherapy. Therefore, the TC-1/dB2m cell line represents a clinically relevant tumor model that may be used for enhancement of cancer immunotherapy.

Název v anglickém jazyce

Establishment and characterization of a mouse tumor cell line with irreversible downregulation of MHC class I molecules

Popis výsledku anglicky

In the majority of human tumors, downregulation of major histocompatibility complex class I (MHC-I) expression contributes to the escape from the host immune system and resistance to immunotherapy. Relevant animal models are therefore needed to enhance the efficacy of cancer immunotherapy. As loss of beta-2 microglobulin expression results in irreversible downregulation of surface MHC-I molecules in various human tumors, the beta-2 microglobulin gene (B2m) was deactivated in a mouse oncogenic TC-1 cell line and a TC-1/dB2m cell line that was negative for surface MHC-I expression was derived. Following stimulation with interferon gamma, MHC-I heavy chains, particularly the H-2D(b) molecules, were found to be expressed at low levels on the cell surface, but without beta-2 microglobulin. B2m deactivation in TC-1/dB2m cells led to reduced proliferation and tumor growth. These cells were insensitive to DNA vaccination and only weakly responsive to combined immunotherapy with a DNA vaccine and the ODN1826 adjuvant. In vivo depletion demonstrated that NK1.1(+) cells were involved in both reduced tumor growth and an antitumor effect of immunotherapy. The number of immune cells infiltrating TC-1/dB2m-induced tumors was comparable with that in tumors developing from TC-1/A9 cells characterized by reversible MHC-I downregulation. However, the composition of the cell infiltrate was different and, most importantly, infiltration with immune cells was not increased in TC-1/dB2m tumors after immunotherapy. Therefore, the TC-1/dB2m cell line represents a clinically relevant tumor model that may be used for enhancement of cancer immunotherapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Oncology Reports

ISSN

1021-335X

e-ISSN

—

Svazek periodika

42

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GR - Řecká republika

Počet stran výsledku

10

Strana od-do

2826-2835

Kód UT WoS článku

000503165000058

EID výsledku v databázi Scopus

2-s2.0-85074619808