Spatial immunoprofiling of retroperitoneal leiomyosarcomas reveals intratumoral heterogeneity in immune cell infiltration, checkpoint molecule expression, and tertiary lymphoid structures

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10504261" target="_blank" >RIV/00064203:_____/25:10504261 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10504261 RIV/00216208:11130/25:10504261

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07853890.2025.2568725" target="_blank" >10.1080/07853890.2025.2568725</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Spatial immunoprofiling of retroperitoneal leiomyosarcomas reveals intratumoral heterogeneity in immune cell infiltration, checkpoint molecule expression, and tertiary lymphoid structures

Popis výsledku v původním jazyce

INTRODUCTION: Leiomyosarcoma (LMS) is a rare, aggressive cancer with limited treatment options at the metastatic stage. The response to immune checkpoint inhibitors (ICIs) is inconsistent, likely due to intratumoral heterogeneity, which is more pronounced in large tumours such as retroperitoneal LMS. METHODS: This study examined heterogeneity in four large treatment-naive LMS tumours (ten samples per tumour) by analysing immune cells, tertiary lymphoid structures (TLSs), checkpoint molecules, and cytokine secretion across different tumour regions. RESULTS: Significant region-dependent differences were observed in immune components, with TLSs present only at tumour margins and inconsistently across samples from the same tumour. Expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) varied within individual tumours, and shared immune patterns were identified in specific regions, including elevated indoleamine 2,3-dioxygenase 1, absence of a particular macrophage subpopulation, and reduced PD-1 and lymphocyte activation gene 3 (LAG-3) expression at organ-adjacent margins. Anti-LAG-3 blockade altered cytokine and checkpoint molecule levels in a region-specific manner. CONCLUSION: These findings highlight substantial intratumoral heterogeneity, which may contribute to the variable response to ICI therapy. As immune checkpoint molecule expression influences treatment eligibility, multiple biopsies from different tumour regions may be necessary to assess immune infiltration accurately and guide therapy decisions.

Název v anglickém jazyce

Spatial immunoprofiling of retroperitoneal leiomyosarcomas reveals intratumoral heterogeneity in immune cell infiltration, checkpoint molecule expression, and tertiary lymphoid structures

Popis výsledku anglicky

INTRODUCTION: Leiomyosarcoma (LMS) is a rare, aggressive cancer with limited treatment options at the metastatic stage. The response to immune checkpoint inhibitors (ICIs) is inconsistent, likely due to intratumoral heterogeneity, which is more pronounced in large tumours such as retroperitoneal LMS. METHODS: This study examined heterogeneity in four large treatment-naive LMS tumours (ten samples per tumour) by analysing immune cells, tertiary lymphoid structures (TLSs), checkpoint molecules, and cytokine secretion across different tumour regions. RESULTS: Significant region-dependent differences were observed in immune components, with TLSs present only at tumour margins and inconsistently across samples from the same tumour. Expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) varied within individual tumours, and shared immune patterns were identified in specific regions, including elevated indoleamine 2,3-dioxygenase 1, absence of a particular macrophage subpopulation, and reduced PD-1 and lymphocyte activation gene 3 (LAG-3) expression at organ-adjacent margins. Anti-LAG-3 blockade altered cytokine and checkpoint molecule levels in a region-specific manner. CONCLUSION: These findings highlight substantial intratumoral heterogeneity, which may contribute to the variable response to ICI therapy. As immune checkpoint molecule expression influences treatment eligibility, multiple biopsies from different tumour regions may be necessary to assess immune infiltration accurately and guide therapy decisions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/NU23J-08-00031" target="_blank" >NU23J-08-00031: Kombinované možnosti léčby měkkotkáňových sarkomů za účelem překonání rezistence k imunoterapii</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Annals of Medicine

ISSN

0785-3890

e-ISSN

1365-2060

Svazek periodika

57

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

21

Strana od-do

2568725

Kód UT WoS článku

001592649500001

EID výsledku v databázi Scopus

2-s2.0-105018527824