Cargando…

Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes

SIMPLE SUMMARY: The tumor immune microenvironment of different breast carcinoma (BC) subtypes and immune gene assembly of metastasizing and non-metastasizing HER2-negative BCs was analyzed. Examination of 309 Hematoxylin and Eosin-stained slides highlighted that the distribution of tumor infiltratin...

Descripción completa

Detalles Bibliográficos
Autores principales: Szeitz, Beáta, Pipek, Orsolya, Kulka, Janina, Szundi, Csilla, Rusz, Orsolya, Tőkés, Tímea, Szász, Attila Marcell, Kovács, Kristóf Attila, Pesti, Adrián, Ben Arie, Taya Beri, Gángó, Ambrus, Fülöp, Zsolt, Drágus, Emőke, Vári-Kakas, Stefan A., Tőkés, Anna Mária
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031175/
https://www.ncbi.nlm.nih.gov/pubmed/35454849
http://dx.doi.org/10.3390/cancers14081942
_version_ 1784692325045239808
author Szeitz, Beáta
Pipek, Orsolya
Kulka, Janina
Szundi, Csilla
Rusz, Orsolya
Tőkés, Tímea
Szász, Attila Marcell
Kovács, Kristóf Attila
Pesti, Adrián
Ben Arie, Taya Beri
Gángó, Ambrus
Fülöp, Zsolt
Drágus, Emőke
Vári-Kakas, Stefan A.
Tőkés, Anna Mária
author_facet Szeitz, Beáta
Pipek, Orsolya
Kulka, Janina
Szundi, Csilla
Rusz, Orsolya
Tőkés, Tímea
Szász, Attila Marcell
Kovács, Kristóf Attila
Pesti, Adrián
Ben Arie, Taya Beri
Gángó, Ambrus
Fülöp, Zsolt
Drágus, Emőke
Vári-Kakas, Stefan A.
Tőkés, Anna Mária
author_sort Szeitz, Beáta
collection PubMed
description SIMPLE SUMMARY: The tumor immune microenvironment of different breast carcinoma (BC) subtypes and immune gene assembly of metastasizing and non-metastasizing HER2-negative BCs was analyzed. Examination of 309 Hematoxylin and Eosin-stained slides highlighted that the distribution of tumor infiltrating lymphocytes (TILs) from peritumoral, stromal and intratumoral regions varied greatly within all subtypes, with most tumors (66.01%) belonging to the immunologically “cold” group. Hormone receptor (HR) negative subtypes generally showed higher immune activity in all analyzed regions. No survival benefit was detected based on the spatial distribution of TILs. A lower CD4(+)/CD8(+) ratio at the stromal internal tumor region indicated longer distant metastasis-free survival. When assessing immune gene expression between metastatic and non-metastatic BCs, the list of differentially expressed genes were non-identical across luminal and TNBCs, suggesting that these subtypes may use different mechanisms to bypass the immunological surveillance. Understanding these differences in the immune gene assembly may pave the way to the development of new immune-modulation therapies. ABSTRACT: We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4(+)/CD8(+) positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4(+)/CD8(+) ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression.
format Online
Article
Text
id pubmed-9031175
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90311752022-04-23 Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes Szeitz, Beáta Pipek, Orsolya Kulka, Janina Szundi, Csilla Rusz, Orsolya Tőkés, Tímea Szász, Attila Marcell Kovács, Kristóf Attila Pesti, Adrián Ben Arie, Taya Beri Gángó, Ambrus Fülöp, Zsolt Drágus, Emőke Vári-Kakas, Stefan A. Tőkés, Anna Mária Cancers (Basel) Article SIMPLE SUMMARY: The tumor immune microenvironment of different breast carcinoma (BC) subtypes and immune gene assembly of metastasizing and non-metastasizing HER2-negative BCs was analyzed. Examination of 309 Hematoxylin and Eosin-stained slides highlighted that the distribution of tumor infiltrating lymphocytes (TILs) from peritumoral, stromal and intratumoral regions varied greatly within all subtypes, with most tumors (66.01%) belonging to the immunologically “cold” group. Hormone receptor (HR) negative subtypes generally showed higher immune activity in all analyzed regions. No survival benefit was detected based on the spatial distribution of TILs. A lower CD4(+)/CD8(+) ratio at the stromal internal tumor region indicated longer distant metastasis-free survival. When assessing immune gene expression between metastatic and non-metastatic BCs, the list of differentially expressed genes were non-identical across luminal and TNBCs, suggesting that these subtypes may use different mechanisms to bypass the immunological surveillance. Understanding these differences in the immune gene assembly may pave the way to the development of new immune-modulation therapies. ABSTRACT: We hypothesized that different BC subtypes are characterized by spatially distinct tumor immune microenvironment (TIME) and that immune gene assembly of metastatic (Met) and non-metastatic (Ctrl) BCs vary across subtypes. Peritumoral, stromal and intratumoral TIL was assessed on 309 BC cases. Hot, cold and immune-excluded groups were defined, and the prognostic role of this classification was assessed. CD4(+)/CD8(+) positivity was analyzed in 75 cases in four systematically predefined tumor regions. Immune gene expression of Met and Ctrl HER2-negative BCs was compared by using NanoString nCounter technology. The amount of TIL infiltration varied greatly within all BC subtypes. Two-third of the cases were cold tumors with no significant survival difference compared to hot tumors. A lower CD4(+)/CD8(+) ratio at the stromal internal tumor region was significantly associated with longer distant metastasis-free survival. The differentially expressed immune genes between Met and Ctrl varied across the studied BC subtypes with TNBC showing distinct features from the luminal subtypes. The TIME is characterized by a considerable heterogeneity; however, low level of TILs does not equate to disease progression. The differences in immune gene expression observed between Met and Ctrl breast carcinomas call attention to the important role of altered immune function in BC progression. MDPI 2022-04-12 /pmc/articles/PMC9031175/ /pubmed/35454849 http://dx.doi.org/10.3390/cancers14081942 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szeitz, Beáta
Pipek, Orsolya
Kulka, Janina
Szundi, Csilla
Rusz, Orsolya
Tőkés, Tímea
Szász, Attila Marcell
Kovács, Kristóf Attila
Pesti, Adrián
Ben Arie, Taya Beri
Gángó, Ambrus
Fülöp, Zsolt
Drágus, Emőke
Vári-Kakas, Stefan A.
Tőkés, Anna Mária
Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title_full Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title_fullStr Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title_full_unstemmed Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title_short Investigating the Prognostic Relevance of Tumor Immune Microenvironment and Immune Gene Assembly in Breast Carcinoma Subtypes
title_sort investigating the prognostic relevance of tumor immune microenvironment and immune gene assembly in breast carcinoma subtypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031175/
https://www.ncbi.nlm.nih.gov/pubmed/35454849
http://dx.doi.org/10.3390/cancers14081942
work_keys_str_mv AT szeitzbeata investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT pipekorsolya investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT kulkajanina investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT szundicsilla investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT ruszorsolya investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT tokestimea investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT szaszattilamarcell investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT kovacskristofattila investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT pestiadrian investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT benarietayaberi investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT gangoambrus investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT fulopzsolt investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT dragusemoke investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT varikakasstefana investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes
AT tokesannamaria investigatingtheprognosticrelevanceoftumorimmunemicroenvironmentandimmunegeneassemblyinbreastcarcinomasubtypes