Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Jahangir CA ，Page DB ，Broeckx G ，Gonzalez CA ，Burke C ，Murphy C ，Reis-Filho JS ，Ly A ，Harms PW ，Gupta RR ，Vieth M ，Hida AI ，Kahila M ，Kos Z ，van Diest PJ ，Verbandt S ，Thagaard J ，Khiroya R ，Abduljabbar K ，Acosta Haab G ，Acs B ，Adams S ，Almeida JS ，Alvarado-Cabrero I ，Azmoudeh-Ardalan F ，Badve S ，Baharun NB ，Bellolio ER ，Bheemaraju V ，Blenman KR ，Botinelly Mendonça Fujimoto L ，Burgues O ，Chardas A ，Cheang MCU ，Ciompi F ，Cooper LA ，Coosemans A ，Corredor G ，Dantas Portela FL ，Deman F ，Demaria S ，Dudgeon SN ，Elghazawy M ，Fernandez-Martín C ，Fineberg S ，Fox SB ，Giltnane JM ，Gnjatic S ，Gonzalez-Ericsson PI ，Grigoriadis A ，Halama N ，Hanna MG ，Harbhajanka A ，Hart SN ，Hartman J ，Hewitt S ，Horlings HM ，Husain Z ，Irshad S ，Janssen EA ，Kataoka TR ，Kawaguchi K ，Khramtsov AI ，Kiraz U ，Kirtani P ，Kodach LL ，Korski K ，Akturk G ，Scott E ，Kovács A ，Laenkholm AV ，Lang-Schwarz C ，Larsimont D ，Lennerz JK ，Lerousseau M ，Li X ，Madabhushi A ，Maley SK ，Manur Narasimhamurthy V ，Marks DK ，McDonald ES ，Mehrotra R ，Michiels S ，Kharidehal D ，Minhas FUAA ，Mittal S ，Moore DA ，Mushtaq S ，Nighat H ，Papathomas T ，Penault-Llorca F ，Perera RD ，Pinard CJ ，Pinto-Cardenas JC ，Pruneri G ，Pusztai L ，Rajpoot NM ，Rapoport BL ，Rau TT ，Ribeiro JM ，Rimm D ，Vincent-Salomon A ，Saltz J ，Sayed S ，Hytopoulos E ，Mahon S ，Siziopikou KP ，Sotiriou C ，Stenzinger A ，Sughayer MA ，Sur D ，Symmans F ，Tanaka S ，Taxter T ，Tejpar S ，Teuwen J ，Thompson EA ，Tramm T ，Tran WT ，van der Laak J ，Verghese GE ，Viale G ，Wahab N ，Walter T ，Waumans Y ，Wen HY ，Yang W ，Yuan Y ，Bartlett J ，Loibl S ，Denkert C ，Savas P ，Loi S ，Specht Stovgaard E ，Salgado R ，Gallagher WM ，Rahman A ... -  《-》

Recent Advances in Pathology: the 2023 Annual Review Issue of The Journal of Pathology.

The 2023 Annual Review Issue of The Journal of Pathology, Recent Advances in Pathology, contains 12 invited reviews on topics of current interest in pathology. This year, our subjects include immuno-oncology and computational pathology approaches for diagnostic and research applications in human disease. Reviews on the tissue microenvironment include the effects of apoptotic cell-derived exosomes, how understanding the tumour microenvironment predicts prognosis, and the growing appreciation of the diverse functions of fibroblast subtypes in health and disease. We also include up-to-date reviews of modern aspects of the molecular basis of malignancies, and our final review covers new knowledge of vascular and lymphatic regeneration in cardiac disease. All of the reviews contained in this issue are written by expert groups of authors selected to discuss the recent progress in their particular fields and all articles are freely available online (https://pathsocjournals.onlinelibrary.wiley.com/journal/10969896). © 2023 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Jones JL ，Poulsom R ，Coates PJ 《-》

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Thagaard J ，Broeckx G ，Page DB ，Jahangir CA ，Verbandt S ，Kos Z ，Gupta R ，Khiroya R ，Abduljabbar K ，Acosta Haab G ，Acs B ，Akturk G ，Almeida JS ，Alvarado-Cabrero I ，Amgad M ，Azmoudeh-Ardalan F ，Badve S ，Baharun NB ，Balslev E ，Bellolio ER ，Bheemaraju V ，Blenman KR ，Botinelly Mendonça Fujimoto L ，Bouchmaa N ，Burgues O ，Chardas A ，Chon U Cheang M ，Ciompi F ，Cooper LA ，Coosemans A ，Corredor G ，Dahl AB ，Dantas Portela FL ，Deman F ，Demaria S ，Doré Hansen J ，Dudgeon SN ，Ebstrup T ，Elghazawy M ，Fernandez-Martín C ，Fox SB ，Gallagher WM ，Giltnane JM ，Gnjatic S ，Gonzalez-Ericsson PI ，Grigoriadis A ，Halama N ，Hanna MG ，Harbhajanka A ，Hart SN ，Hartman J ，Hauberg S ，Hewitt S ，Hida AI ，Horlings HM ，Husain Z ，Hytopoulos E ，Irshad S ，Janssen EA ，Kahila M ，Kataoka TR ，Kawaguchi K ，Kharidehal D ，Khramtsov AI ，Kiraz U ，Kirtani P ，Kodach LL ，Korski K ，Kovács A ，Laenkholm AV ，Lang-Schwarz C ，Larsimont D ，Lennerz JK ，Lerousseau M ，Li X ，Ly A ，Madabhushi A ，Maley SK ，Manur Narasimhamurthy V ，Marks DK ，McDonald ES ，Mehrotra R ，Michiels S ，Minhas FUAA ，Mittal S ，Moore DA ，Mushtaq S ，Nighat H ，Papathomas T ，Penault-Llorca F ，Perera RD ，Pinard CJ ，Pinto-Cardenas JC ，Pruneri G ，Pusztai L ，Rahman A ，Rajpoot NM ，Rapoport BL ，Rau TT ，Reis-Filho JS ，Ribeiro JM ，Rimm D ，Roslind A ，Vincent-Salomon A ，Salto-Tellez M ，Saltz J ，Sayed S ，Scott E ，Siziopikou KP ，Sotiriou C ，Stenzinger A ，Sughayer MA ，Sur D ，Fineberg S ，Symmans F ，Tanaka S ，Taxter T ，Tejpar S ，Teuwen J ，Thompson EA ，Tramm T ，Tran WT ，van der Laak J ，van Diest PJ ，Verghese GE ，Viale G ，Vieth M ，Wahab N ，Walter T ，Waumans Y ，Wen HY ，Yang W ，Yuan Y ，Zin RM ，Adams S ，Bartlett J ，Loibl S ，Denkert C ，Savas P ，Loi S ，Salgado R ，Specht Stovgaard E ... -  《-》

Multiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists.

Our understanding of the biology and management of human disease has undergone a remarkable evolution in recent decades. Improved understanding of the roles of complex immune populations in the tumor microenvironment has advanced our knowledge of antitumor immunity, and immunotherapy has radically improved outcomes for many advanced cancers. Digital pathology has unlocked new possibilities for the assessment and discovery of the tumor microenvironment, such as quantitative and spatial image analysis. Despite these advances, tissue-based evaluations for diagnosis and prognosis continue to rely on traditional practices, such as hematoxylin and eosin staining, supplemented by the assessment of single biomarkers largely using chromogenic immunohistochemistry (IHC). Such approaches are poorly suited to complex quantitative analyses and the simultaneous evaluation of multiple biomarkers. Thus, multiplex staining techniques have significant potential to improve diagnostic practice and immuno-oncology research. The different approaches to achieve multiplexed IHC and immunofluorescence are described in this study. Alternatives to multiplex immunofluorescence/IHC include epitope-based tissue mass spectrometry and digital spatial profiling (DSP), which require specialized platforms not available to most clinical laboratories. Virtual multiplexing, which involves digitally coregistering singleplex IHC stains performed on serial sections, is another alternative to multiplex staining. Regardless of the approach, analysis of multiplexed stains sequentially or simultaneously will benefit from standardized protocols and digital pathology workflows. Although this is a complex and rapidly advancing field, multiplex staining is now technically feasible for most clinical laboratories and may soon be leveraged for routine diagnostic use. This review provides an update on the current state of the art for tissue multiplexing, including the capabilities and limitations of different techniques, with an emphasis on potential relevance to clinical diagnostic practice.

Harms PW ，Frankel TL ，Moutafi M ，Rao A ，Rimm DL ，Taube JM ，Thomas D ，Chan MP ，Pantanowitz L ... -  《-》

Delineating the breast cancer immune microenvironment in the era of multiplex immunohistochemistry/immunofluorescence.

Breast cancer is the most common malignancy and the leading cause of cancer death in females worldwide. Treatment is challenging, especially for those who are triple-negative. Increasing evidence suggests that diverse immune populations are present in the breast tumour microenvironment, which opens up avenues for personalised drug targets. Historically, our investigations into the immune constitution of breast tumours have been restricted to analyses of one or two markers at a given time. Recent technological advances have allowed simultaneous labelling of more than 35 markers and detailed profiling of tumour-immune infiltrates at the single-cell level, as well as determining the cellular composition and spatial analysis of the entire tumour architecture. In this review, we describe emerging technologies that have contributed to the field of breast cancer diagnosis, and discuss how to interpret the vast data sets obtained in order to effectively translate them for clinically relevant use.

Tien TZ ，Lee JNLW ，Lim JCT ，Chen XY ，Thike AA ，Tan PH ，Yeong JPS ... -  《-》