IL-7/alpha IL-7 mAb M25 immunocomplexes expand CD8(+) T cells but paradoxically abrogate the antitumor activity of CTLA-4 and PD-1 blockage

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00531980" target="_blank" >RIV/61388971:_____/20:00531980 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S1043466620301903" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1043466620301903</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cyto.2020.155174" target="_blank" >10.1016/j.cyto.2020.155174</a>

Jazyk výsledku

angličtina

Název v původním jazyce

IL-7/alpha IL-7 mAb M25 immunocomplexes expand CD8(+) T cells but paradoxically abrogate the antitumor activity of CTLA-4 and PD-1 blockage

Popis výsledku v původním jazyce

Supraphysiological levels of IL-7 induce increase counts of pre-B cells, naive T cells and memory phenotype CD8(+) T cells. Immunocomplexes of IL-7 and alpha IL-7 mAb M25 (IL-7/M25) were described as IL-7 superagonist in vivo. Thus, treatment of mice with IL-7/M25 remarkably increases the size of the T cell pool. We decided to use IL-7/M25 in order to expand the T cell population prior to the administration of alpha CTLA-4 and alpha PD-1 mAbs in tumor-bearing mice and in turn boost the immunotherapy based on a combination of CTLA-4 and PD-1 blockage. We found that just four doses of IL-7/M25 increased the absolute numbers of splenocytes approximately fivefold and significantly shifted the CD4(+):CD8(+) T cell ratio in favor of CD8(+) T cells. There was also a substantive increase in relative counts of memory phenotype CD8(+) T cells (approximately threefold) within CD8(+) T cells but a significant decrease (approximately 30%) in relative counts of Treg cells within CD4(+) T cells. All these data suggest that IL-7/M25 offer a suitable approach to potentiate tumor immunotherapy through CTLA-4 and PD-1 blockage. Unexpectedly, IL-7/M25 significantly abrogated the antitumor activity of alpha CTLA-4 plus alpha PD-1 mAbs in the following mouse tumor models: MC-38 and CT26 colon carcinoma and B16F10 melanoma. This paradoxical effect of IL-7/M25 on the antitumor activity of CTLA-4 and PD-1 blockage was not mediated via either increased levels of IL-10 or TGF-beta in the sera or increased counts of IL-10-producing B or T cells in the spleen of mice injected with IL-7/M25. Thus, our work shows that caution should be exercised when combining two immunotherapy approaches together.

Název v anglickém jazyce

IL-7/alpha IL-7 mAb M25 immunocomplexes expand CD8(+) T cells but paradoxically abrogate the antitumor activity of CTLA-4 and PD-1 blockage

Popis výsledku anglicky

Supraphysiological levels of IL-7 induce increase counts of pre-B cells, naive T cells and memory phenotype CD8(+) T cells. Immunocomplexes of IL-7 and alpha IL-7 mAb M25 (IL-7/M25) were described as IL-7 superagonist in vivo. Thus, treatment of mice with IL-7/M25 remarkably increases the size of the T cell pool. We decided to use IL-7/M25 in order to expand the T cell population prior to the administration of alpha CTLA-4 and alpha PD-1 mAbs in tumor-bearing mice and in turn boost the immunotherapy based on a combination of CTLA-4 and PD-1 blockage. We found that just four doses of IL-7/M25 increased the absolute numbers of splenocytes approximately fivefold and significantly shifted the CD4(+):CD8(+) T cell ratio in favor of CD8(+) T cells. There was also a substantive increase in relative counts of memory phenotype CD8(+) T cells (approximately threefold) within CD8(+) T cells but a significant decrease (approximately 30%) in relative counts of Treg cells within CD4(+) T cells. All these data suggest that IL-7/M25 offer a suitable approach to potentiate tumor immunotherapy through CTLA-4 and PD-1 blockage. Unexpectedly, IL-7/M25 significantly abrogated the antitumor activity of alpha CTLA-4 plus alpha PD-1 mAbs in the following mouse tumor models: MC-38 and CT26 colon carcinoma and B16F10 melanoma. This paradoxical effect of IL-7/M25 on the antitumor activity of CTLA-4 and PD-1 blockage was not mediated via either increased levels of IL-10 or TGF-beta in the sera or increased counts of IL-10-producing B or T cells in the spleen of mice injected with IL-7/M25. Thus, our work shows that caution should be exercised when combining two immunotherapy approaches together.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/GA18-12973S" target="_blank" >GA18-12973S: Komplexy IL-2 s muteiny mAb JES6-1 mající různou afinitou k IL-2: hledání varianty s nejvíce selektivní stimulační aktivitou pro Treg buňky in vivo</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

CYTOKINE

ISSN

1096-0023

e-ISSN

—

Svazek periodika

133

Číslo periodika v rámci svazku

SEP 2020

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

155174

Kód UT WoS článku

000554002300039

EID výsledku v databázi Scopus

2-s2.0-85086867663