A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate anti-PD-1 blockade

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083960" target="_blank" >RIV/00023001:_____/23:00083960 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/23:10446022 RIV/00216208:11110/23:10446022 RIV/00064203:_____/23:10446022

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00432-022-04292-8" target="_blank" >https://link.springer.com/article/10.1007/s00432-022-04292-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00432-022-04292-8" target="_blank" >10.1007/s00432-022-04292-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate anti-PD-1 blockade

Popis výsledku v původním jazyce

Purpose The treatment options for metastatic soft tissue sarcomas (STSs) are limited. In most cases, immunotherapy with immune checkpoint inhibitors has not been successful so far. Macrophages dominate the immune landscape of STSs; thus, combinatorial strategies aiming at both tumor-infiltrating lymphocytes and macrophages may represent a particularly relevant treatment approach for metastatic or recurrent STSs. Methods In this cohort study, 66 patients who underwent surgery for STSs were enrolled. Tumor cells and tumor-infiltrating immune cells were analyzed using flow cytometry and immunohistochemistry. In cell suspensions obtained from surgical resections, human T cells were activated by superparamagnetic polymer beads and cultured at a concentration of 0.3 x 10(6)/mu l in the absence or presence of therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, and anti-PD-1 + anti-CD47). Supernatants from cell suspensions were analyzed using multiplex Luminex cytokine bead-based immunoassays. Results The most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma which also displayed high expression of CD47 in the tumor microenvironment. Both anti-PD-1 and anti-CD47 therapies drastically increased the production of pro-inflammatory cytokines in the tumor microenvironment of STSs, but co-administration of both agents did not further increase cytokine secretion. Furthermore, all patient samples treated with a combination of both anti-PD-1 and anti-CD47 antibodies showed a dramatic reduction in cytokine secretion. Conclusion Our findings suggest that anti-PD-1 and anti-CD47 therapies do not enhance each other, and the combined application of anti-PD-1 and anti-CD47 agents in vitro limits rather than potentiates their efficacy.

Název v anglickém jazyce

A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate anti-PD-1 blockade

Popis výsledku anglicky

Purpose The treatment options for metastatic soft tissue sarcomas (STSs) are limited. In most cases, immunotherapy with immune checkpoint inhibitors has not been successful so far. Macrophages dominate the immune landscape of STSs; thus, combinatorial strategies aiming at both tumor-infiltrating lymphocytes and macrophages may represent a particularly relevant treatment approach for metastatic or recurrent STSs. Methods In this cohort study, 66 patients who underwent surgery for STSs were enrolled. Tumor cells and tumor-infiltrating immune cells were analyzed using flow cytometry and immunohistochemistry. In cell suspensions obtained from surgical resections, human T cells were activated by superparamagnetic polymer beads and cultured at a concentration of 0.3 x 10(6)/mu l in the absence or presence of therapeutic monoclonal antibodies (anti-PD-1, anti-CD47, and anti-PD-1 + anti-CD47). Supernatants from cell suspensions were analyzed using multiplex Luminex cytokine bead-based immunoassays. Results The most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma which also displayed high expression of CD47 in the tumor microenvironment. Both anti-PD-1 and anti-CD47 therapies drastically increased the production of pro-inflammatory cytokines in the tumor microenvironment of STSs, but co-administration of both agents did not further increase cytokine secretion. Furthermore, all patient samples treated with a combination of both anti-PD-1 and anti-CD47 antibodies showed a dramatic reduction in cytokine secretion. Conclusion Our findings suggest that anti-PD-1 and anti-CD47 therapies do not enhance each other, and the combined application of anti-PD-1 and anti-CD47 agents in vitro limits rather than potentiates their efficacy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of cancer research and clinical oncology

ISSN

0171-5216

e-ISSN

1432-1335

Svazek periodika

149

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

3789-3801

Kód UT WoS článku

000843358000002

EID výsledku v databázi Scopus

2-s2.0-85136550053