An autologous dendritic cell vaccine promotes anticancer immunity in patients with ovarian cancer with low mutational burden and cold tumors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10443830" target="_blank" >RIV/00064165:_____/22:10443830 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064173:_____/22:43923571 RIV/00064203:_____/22:10443830 RIV/00216208:11110/22:10443830 RIV/00216208:11120/22:43923571 a 4 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9V6.YOjM1G" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9V6.YOjM1G</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1078-0432.CCR-21-4413" target="_blank" >10.1158/1078-0432.CCR-21-4413</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An autologous dendritic cell vaccine promotes anticancer immunity in patients with ovarian cancer with low mutational burden and cold tumors

Popis výsledku v původním jazyce

PURPOSE: The successful implementation of immune checkpoint inhibitors (ICIs) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunological features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized Phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937). EXPERIMENTAL DESIGN: We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, immunohistochemistry to analyze (pre-treatment) tumor and (pre-treatment and post-treatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunological biomarkers that would improve the clinical management of patients with EOC treated with DCVAC. RESULTS: Although higher-than-median TMB and abundant CD8+ T cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood. CONCLUSIONS: Our findings suggest that while patients with highly infiltrated, &quot;hot&quot; EOCs benefit from chemotherapy, women with &quot;cold&quot; EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.

Název v anglickém jazyce

An autologous dendritic cell vaccine promotes anticancer immunity in patients with ovarian cancer with low mutational burden and cold tumors

Popis výsledku anglicky

PURPOSE: The successful implementation of immune checkpoint inhibitors (ICIs) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunological features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized Phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937). EXPERIMENTAL DESIGN: We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, immunohistochemistry to analyze (pre-treatment) tumor and (pre-treatment and post-treatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunological biomarkers that would improve the clinical management of patients with EOC treated with DCVAC. RESULTS: Although higher-than-median TMB and abundant CD8+ T cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood. CONCLUSIONS: Our findings suggest that while patients with highly infiltrated, &quot;hot&quot; EOCs benefit from chemotherapy, women with &quot;cold&quot; EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Clinical Cancer Research

ISSN

1078-0432

e-ISSN

1557-3265

Svazek periodika

28

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

3053-3065

Kód UT WoS článku

000831792700001

EID výsledku v databázi Scopus

2-s2.0-85133491597