Cargando…
An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy
Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFβ activity and signaling as a determinant of T cell exclusion in the tumor microe...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513441/ https://www.ncbi.nlm.nih.gov/pubmed/36176910 http://dx.doi.org/10.1016/j.apsb.2022.03.013 |
_version_ | 1784798063888433152 |
---|---|
author | Pomponio, Robert Tang, Qi Mei, Anthony Caron, Anne Coulibaly, Bema Theilhaber, Joachim Rogers-Grazado, Maximilian Sanicola-Nadel, Michele Naimi, Souad Olfati-Saber, Reza Combeau, Cecile Pollard, Jack Lin, Tun Tun Wang, Rui |
author_facet | Pomponio, Robert Tang, Qi Mei, Anthony Caron, Anne Coulibaly, Bema Theilhaber, Joachim Rogers-Grazado, Maximilian Sanicola-Nadel, Michele Naimi, Souad Olfati-Saber, Reza Combeau, Cecile Pollard, Jack Lin, Tun Tun Wang, Rui |
author_sort | Pomponio, Robert |
collection | PubMed |
description | Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFβ activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβ pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβ pathway activation, together with elevated TGFβ signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between “cold” tumor-immune phenotypes and TGFβ signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβ blockade. |
format | Online Article Text |
id | pubmed-9513441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-95134412022-09-28 An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy Pomponio, Robert Tang, Qi Mei, Anthony Caron, Anne Coulibaly, Bema Theilhaber, Joachim Rogers-Grazado, Maximilian Sanicola-Nadel, Michele Naimi, Souad Olfati-Saber, Reza Combeau, Cecile Pollard, Jack Lin, Tun Tun Wang, Rui Acta Pharm Sin B Tools Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFβ activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβ pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβ pathway activation, together with elevated TGFβ signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between “cold” tumor-immune phenotypes and TGFβ signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβ blockade. Elsevier 2022-09 2022-03-25 /pmc/articles/PMC9513441/ /pubmed/36176910 http://dx.doi.org/10.1016/j.apsb.2022.03.013 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Tools Pomponio, Robert Tang, Qi Mei, Anthony Caron, Anne Coulibaly, Bema Theilhaber, Joachim Rogers-Grazado, Maximilian Sanicola-Nadel, Michele Naimi, Souad Olfati-Saber, Reza Combeau, Cecile Pollard, Jack Lin, Tun Tun Wang, Rui An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title | An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title_full | An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title_fullStr | An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title_full_unstemmed | An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title_short | An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβ blockade therapy |
title_sort | integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for tgfβ blockade therapy |
topic | Tools |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513441/ https://www.ncbi.nlm.nih.gov/pubmed/36176910 http://dx.doi.org/10.1016/j.apsb.2022.03.013 |
work_keys_str_mv | AT pomponiorobert anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT tangqi anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT meianthony anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT caronanne anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT coulibalybema anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT theilhaberjoachim anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT rogersgrazadomaximilian anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT sanicolanadelmichele anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT naimisouad anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT olfatisaberreza anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT combeaucecile anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT pollardjack anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT lintuntun anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT wangrui anintegrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT pomponiorobert integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT tangqi integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT meianthony integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT caronanne integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT coulibalybema integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT theilhaberjoachim integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT rogersgrazadomaximilian integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT sanicolanadelmichele integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT naimisouad integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT olfatisaberreza integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT combeaucecile integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT pollardjack integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT lintuntun integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy AT wangrui integrativeapproachofdigitalimageanalysisandtranscriptomeprofilingtoexplorepotentialpredictivebiomarkersfortgfbblockadetherapy |