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Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.

ABSTRACT: BACKGROUND:Breast cancer (BC) immune infiltrates play a critical role in tumor progression and response to treatment. Besides stromal tumor infiltrating lymphocytes (sTILs) which have recently reached level 1B evidence as a prognostic marker in triple negative BC, a plethora of methods to assess immune infiltration exists, and it is unclear how these compare to each other and if they can be used interchangeably. METHODS:Two experienced pathologists scored sTIL, intra-tumoral TIL (itTIL), and 6 immune cell types (CD3+, CD4+, CD8+, CD20+, CD68+, FOXP3+) in the International Cancer Genomics Consortium breast cancer cohort using hematoxylin and eosin-stained (n?=?243) and immunohistochemistry-stained tissue microarrays (n?=?254) and whole slides (n?=?82). The same traits were evaluated using transcriptomic- and methylomic-based deconvolution methods or signatures. RESULTS:The concordance correlation coefficient (CCC) between pathologists for sTIL was very good (0.84) and for cell-specific immune infiltrates slightly lower (0.63-0.66). Comparison between tissue microarray and whole slide pathology scores revealed systematically higher values in whole slides (ratio 2.60-5.98). The Spearman correlations between microscopic sTIL and transcriptomic- or methylomic-based assessment of immune infiltrates were highly variable (r?=?0.01-0.56). Similar observations were made for cell type-specific quantifications (r?=?0.001-0.54). We observed a strong inter-method variability between the omics-derived estimations, which is further cell type dependent. Finally, we demonstrated that most methods more accurately identify highly infiltrated (sTIL???60%; area under the curve, AUC, 0.64-0.99) as compared to lowly infiltrated tumors (sTIL???10%; AUC 0.52-0.82). CONCLUSIONS:There is a lower inter-pathologist concordance for cell-specific quantification as compared to overall infiltration quantification. Microscopic assessments are underestimated when considering small cores (tissue microarray) instead of whole slides. Results further highlight considerable differences between the microscopic-, transcriptomic-, and methylomic-based methods in the assessment of overall and cell-specific immune infiltration in BC. We therefore call for extreme caution when assessing immune infiltrates using current methods and emphasize the need for standardized immune characterization beyond TIL.

SUBMITTER: Nederlof I

PROVIDER: S-EPMC6933637 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.

Nederlof Iris I De Bortoli Davide D Bareche Yacine Y Nguyen Bastien B de Maaker Michiel M Hooijer Gerrit K J GKJ Buisseret Laurence L Kok Marleen M Smid Marcel M Van den Eynden Gert G G M GGGM Brinkman Arie B AB Hudecek Jan J Koster Jan J Sotiriou Christos C Larsimont Denis D Martens John W M JWM van de Vijver Marc J MJ Horlings Hugo M HM Salgado Roberto R Biganzoli Elia E Desmedt Christine C

Breast cancer research : BCR 20191226 1

<h4>Background</h4>Breast cancer (BC) immune infiltrates play a critical role in tumor progression and response to treatment. Besides stromal tumor infiltrating lymphocytes (sTILs) which have recently reached level 1B evidence as a prognostic marker in triple negative BC, a plethora of methods to assess immune infiltration exists, and it is unclear how these compare to each other and if they can be used interchangeably.<h4>Methods</h4>Two experienced pathologists scored sTIL, intra-tumoral TIL ( ...[more]

PMID: 31878981

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Dataset Information

Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.

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Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.

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