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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/NU20-03-00477" target="_blank" >NU20-03-00477: Smart biokompatabilní nanonástroje pro selektivní doručení drug-siRNA koktejlů pro kombinovanou terapii rakoviny prsu</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Chemical Engineering Journal

ISSN

1385-8947

e-ISSN

1873-3212

Svazek periodika

466

Číslo periodika v rámci svazku

15 June

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

18

Strana od-do

142956

Kód UT WoS článku

000989226400001

EID výsledku v databázi Scopus

2-s2.0-85153795199