A "2+2" Strategy for Tumor Immune Microenvironment Remodeling Based on Complementary Immune Checkpoint Blockade

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F23%3A43923373" target="_blank" >RIV/62156489:43210/23:43923373 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.cej.2023.142956" target="_blank" >https://doi.org/10.1016/j.cej.2023.142956</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cej.2023.142956" target="_blank" >10.1016/j.cej.2023.142956</a>

Result language

angličtina

Original language name

A "2+2" Strategy for Tumor Immune Microenvironment Remodeling Based on Complementary Immune Checkpoint Blockade

Original language description

Despite a clinical success of cancer immunotherapy, its efficacy is often limited due to immune resistance and insufficient immune response induced by the tumor immune microenvironment (TIME). Thus, further appropriate interventions are needed to reshape the immune microenvironment to maintain an effective and durable immune response. Herein, we report that a strategy involving complementary immune checkpoint blockade of ADAR1 and PD-1 can enhance the immune response and decrease the rate of immune evasion by regulating the TIME. We first designed a charge-reversible nanosystem, named Au-PEI/shADAR1/PEI-citraconic anhydride (AAPC), to effectively deliver shADAR1 to inhibit expression of the ADAR1, a potential immune checkpoint in tumor cells. Then, we demonstrated a simultaneous decrease in immune escape and activation of antitumor immunity in tumor-bearing mice upon combined treatment with AAPC and an anti-PD-1 antibody, an immune checkpoint blockade acts on T cells; this combination therapy was more efficacious than either treatment alone. Additionally, mechanistic and transcriptomic analysis confirmed that complementary immune checkpoint blockade regulated the abundance of immune cells. Finally, combined with X-ray irradiation, a &quot;2+2&quot; strategy involving combined dual normalization (&quot;2&quot;, dsRNA sensitization and anti-PD therapy) and dual enhancement (&quot;2&quot;, antigen presentation by radiotherapy and immunogenetic cell death induced by MDA5 activation) immunotherapy efficiently reshaped the TIME by regulating a variety of immune cells.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NU20-03-00477" target="_blank" >NU20-03-00477: Smart biocompatible nanotools for a selective delivery of drug-siRNA cocktails for combination therapy of breast cancer</a><br>

Continuities

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

Publication year

2023

Confidentiality

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

Name of the periodical

Chemical Engineering Journal

ISSN

1385-8947

e-ISSN

1873-3212

Volume of the periodical

466

Issue of the periodical within the volume

15 June

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

18

Pages from-to

142956

UT code for WoS article

000989226400001

EID of the result in the Scopus database

2-s2.0-85153795199