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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10606 - Microbiology

Project

<a href="/en/project/GA18-12973S" target="_blank" >GA18-12973S: IL-2 complexed with muteins of JES6-1 mAb having different affinity to IL-2: finding variant with most selective stimulation of Treg cells in vivo</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

CYTOKINE

ISSN

1096-0023

e-ISSN

—

Volume of the periodical

133

Issue of the periodical within the volume

SEP 2020

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

155174

UT code for WoS article

000554002300039

EID of the result in the Scopus database

2-s2.0-85086867663