Experimental Combined Immunotherapy of Tumours with Major Histocompatibility Complex Class I Downregulation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10385887" target="_blank" >RIV/00216208:11310/18:10385887 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.3390/ijms19113693" target="_blank" >https://doi.org/10.3390/ijms19113693</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms19113693" target="_blank" >10.3390/ijms19113693</a>

Result language

angličtina

Original language name

Experimental Combined Immunotherapy of Tumours with Major Histocompatibility Complex Class I Downregulation

Original language description

Combined immunotherapy constitutes a novel, advanced strategy in cancer treatment. In this study, we investigated immunotherapy in the mouse TC-1/A9 model of human papillomavirus type 16 (HPV16)-associated tumors characterized by major histocompatibility complex class I (MHC-I) downregulation. We found that the induction of a significant anti-tumor response required a combination of DNA vaccination with the administration of an adjuvant, either the synthetic oligodeoxynucleotide ODN1826, carrying immunostimulatory CpG motifs, or -galactosylceramide (-GalCer). The most profound anti-tumor effect was achieved when these adjuvants were applied in a mix with a one-week delay relative to DNA immunization. Combined immunotherapy induced tumor infiltration with various subsets of immune cells contributing to tumor regression, of which cluster of differentiation (CD) 8(+) T cells were the predominant subpopulation. In contrast, the numbers of tumor-associated macrophages (TAMs) were not markedly increased after immunotherapy but in vivo and in vitro results showed that they could be repolarized to an anti-tumor M1 phenotype. A blockade of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) immune checkpoint had a negligible effect on anti-tumor immunity and TAMs repolarization. Our results demonstrate a benefit of combined immunotherapy comprising the activation of both adaptive and innate immunity in the treatment of tumors with reduced MHC-I expression.

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

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OECD FORD branch

10600 - Biological sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

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Volume of the periodical

19

Issue of the periodical within the volume

11

Country of publishing house

CH - SWITZERLAND

Number of pages

21

Pages from-to

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UT code for WoS article

000451528500409

EID of the result in the Scopus database

2-s2.0-85057082653