Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Zuzana Kos , Elvire Roblin (1) , Rim Kim , Stefan Michiels (2, 3, 1, 4) , Brandon Gallas , Weijie Chen , Koen van de Vijver , Shom Goel , Sylvia Adams , Sandra Demaria , Giuseppe Viale (5) , Torsten Nielsen , Sunil Badve , W Fraser Symmans , Christos Sotiriou (6) , David Rimm , Stephen Hewitt , Carsten Denkert (7) , Sibylle Loibl (8) , Stephen Luen , John Bartlett (9) , Peter Savas , Giancarlo Pruneri (10) , Deborah Dillon , Maggie Chon U Cheang , Andrew Tutt (11) , Jacqueline Hall , Marleen Kok (12) , Hugo Horlings (13) , Anant Madabhushi , Jeroen van Der Laak , Francesco Ciompi , Anne-Vibeke Laenkholm (14) , Enrique Bellolio , Tina Gruosso (15) , Stephen Fox , Juan Carlos Araya , Giuseppe Floris , Jan Hudeček , Leonie Voorwerk , Andrew Beck , Jen Kerner , Denis Larsimont (6) , Sabine Declercq , Gert van den Eynden , Lajos Pusztai (16) , Anna Ehinger (17) , Wentao Yang , Khalid Abduljabbar , Yinyin Yuan , Rajendra Singh , Crispin Hiley , Maise Al Bakir , Alexander J Lazar (18) , Stephen Naber , Stephan Wienert , Miluska Castillo , Giuseppe Curigliano (19) , Maria-Vittoria Dieci , Fabrice André (3, 20) , Charles Swanton (21) , Jorge Reis-Filho (22) , Joseph Sparano , Eva Balslev (23) , I-Chun Chen , Elisabeth Ida Specht Stovgaard , Katherine Pogue-Geile , Kim Blenman , Frédérique Penault-Llorca (24, 25) , Stuart Schnitt , Sunil R Lakhani (26) , Anne Vincent-Salomon (27) , Federico Rojo (28) , Jeremy Braybrooke , Matthew Hanna , M Teresa Soler-Monsó , Daniel Bethmann , Carlos Castaneda (29) , Karen Willard-Gallo , Ashish Sharma (30) , Huang-Chun Lien , Susan Fineberg , Jeppe Thagaard , Laura Comerma , Paula Gonzalez-Ericsson , Edi Brogi , Sherene Loi (31) , Joel Saltz , Frederick Klaushen , Lee Cooper , Mohamed Amgad , David Moore (32) , Roberto Salgado (31) , W. Fraser Symmans , Maggie Chon U. Cheang , M. Teresa Soler-Monsó

1 CESP - Centre de recherche en épidémiologie et santé des populations
2 SBE - Service de biostatistique et d'épidémiologie
3 IGR - Institut Gustave Roussy
4 U1018 (Équipe 2) - Oncostat
5 Division of Pathology and Laboratory Medicine
6 Institut Jules Bordet [Bruxelles]
7 Charité, Institute of Pathology, Translational Tumorpathology Unit
8 GBG - German Breast Group
9 USC - University of the Sunshine Coast
10 ESMO - European Institute of Oncology [Milan]
11 Breakthrough Breast Cancer Centre
12 Department of Pathology
13 Division of Experimental Therapy
14 Department of Pathology
15 U830 - Unité de génétique et biologie des cancers
16 Department of Breast Medical Oncology [Houston]
17 Department of Pathology
18 The University of Texas M.D. Anderson Cancer Center [Houston]
19 Division of Experimental Therapeutics [Milan, Italy]
20 Département de médecine oncologique [Gustave Roussy]
21 Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni]
22 Memorial Sloane Kettering Cancer Center [New York]
23 Department of Pathology
24 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
25 IMoST - Imagerie Moléculaire et Stratégies Théranostiques
26 USQ - University of Southern Queensland
27 Unité de Pharmacogénomique [Institut Curie]
28 IFT - Instituto de Física Teórica UAM/CSIC
29 Ctr Biomol Struct & Org
30 The University of Sydney
31 Breast Cancer Translational Research Laboratory
32 Innovation North - Faculty of Information and Technology

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

Mots clés: Immunosurveillance; Prognostic markers

Domaines: Sciences du Vivant [q-bio]; Cancer

Zuzana Kos, Elvire Roblin, Rim Kim, Stefan Michiels, Brandon Gallas, et al.. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. npj Breast Cancer, 2020, 6 (1), pp.17. ⟨10.1038/s41523-020-0156-0⟩. ⟨hal-02882217⟩