BACKGROUND: CD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell population and clinical implications of TIL accumulation before and after CRT. METHODS: We recruited 93 rectal cancer patients who underwent neoadjuvant CRT and radical resection. Pretreatment biopsy and post-CRT resected specimens were immunostained for CD8 and FOXP3, and the densities of stromal (STL) and intraepithelial (IEL) immunopositive TILs were determined separately. In addition, 54 patients with resections but without neoadjuvant CRT were enrolled for comparison. RESULTS: CD8+ STL density doubled after CRT (average counts: 92 vs. 230 per microscopic field using a 20 × objective lens; P < 0.0001), whereas FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT CD8 + STL density was associated with better prognosis (5-year recurrence-free survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL ratio was a predictor of favorable tumor regression (P = 0.0029). CONCLUSIONS: Favorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome.
BACKGROUND:CD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed. We investigated whether neoadjuvant CRT altered the in situ immune cell population and clinical implications of TIL accumulation before and after CRT. METHODS: We recruited 93 rectal cancerpatients who underwent neoadjuvant CRT and radical resection. Pretreatment biopsy and post-CRT resected specimens were immunostained for CD8 and FOXP3, and the densities of stromal (STL) and intraepithelial (IEL) immunopositive TILs were determined separately. In addition, 54 patients with resections but without neoadjuvant CRT were enrolled for comparison. RESULTS:CD8+ STL density doubled after CRT (average counts: 92 vs. 230 per microscopic field using a 20 × objective lens; P < 0.0001), whereas FOXP3+ STL counts remained stable (109 vs. 109). Compared with non-CRT cases, CRT increased CD8+ STL density. Multivariate analyses demonstrated that high post-CRT CD8 + STL density was associated with better prognosis (5-year recurrence-free survival: 87.5 vs. 57.8 %; P = 0.0058) and that a high pretreatment CD8/FOXP3 IEL ratio was a predictor of favorable tumor regression (P = 0.0029). CONCLUSIONS: Favorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome.
Authors: Shona Hendry; Roberto Salgado; Thomas Gevaert; Prudence A Russell; Tom John; Bibhusal Thapa; Michael Christie; Koen van de Vijver; M V Estrada; Paula I Gonzalez-Ericsson; Melinda Sanders; Benjamin Solomon; Cinzia Solinas; Gert G G M Van den Eynden; Yves Allory; Matthias Preusser; Johannes Hainfellner; Giancarlo Pruneri; Andrea Vingiani; Sandra Demaria; Fraser Symmans; Paolo Nuciforo; Laura Comerma; E A Thompson; Sunil Lakhani; Seong-Rim Kim; Stuart Schnitt; Cecile Colpaert; Christos Sotiriou; Stefan J Scherer; Michail Ignatiadis; Sunil Badve; Robert H Pierce; Giuseppe Viale; Nicolas Sirtaine; Frederique Penault-Llorca; Tomohagu Sugie; Susan Fineberg; Soonmyung Paik; Ashok Srinivasan; Andrea Richardson; Yihong Wang; Ewa Chmielik; Jane Brock; Douglas B Johnson; Justin Balko; Stephan Wienert; Veerle Bossuyt; Stefan Michiels; Nils Ternes; Nicole Burchardi; Stephen J Luen; Peter Savas; Frederick Klauschen; Peter H Watson; Brad H Nelson; Carmen Criscitiello; Sandra O'Toole; Denis Larsimont; Roland de Wind; Giuseppe Curigliano; Fabrice André; Magali Lacroix-Triki; Mark van de Vijver; Federico Rojo; Giuseppe Floris; Shahinaz Bedri; Joseph Sparano; David Rimm; Torsten Nielsen; Zuzana Kos; Stephen Hewitt; Baljit Singh; Gelareh Farshid; Sibylle Loibl; Kimberly H Allison; Nadine Tung; Sylvia Adams; Karen Willard-Gallo; Hugo M Horlings; Leena Gandhi; Andre Moreira; Fred Hirsch; Maria V Dieci; Maria Urbanowicz; Iva Brcic; Konstanty Korski; Fabien Gaire; Hartmut Koeppen; Amy Lo; Jennifer Giltnane; Marlon C Rebelatto; Keith E Steele; Jiping Zha; Kenneth Emancipator; Jonathan W Juco; Carsten Denkert; Jorge Reis-Filho; Sherene Loi; Stephen B Fox Journal: Adv Anat Pathol Date: 2017-11 Impact factor: 3.875
Authors: Constance Le Goux; Sophie Vacher; Géraldine Pignot; Mathilde Sibony; Nicolas Barry Delongchamps; Benoit Terris; Eliane Piaggio; Marc Zerbib; Diane Damotte; Ivan Bieche Journal: Oncoimmunology Date: 2017-08-14 Impact factor: 8.110
Authors: C Mirjolet; C Charon-Barra; S Ladoire; F Arbez-Gindre; A Bertaut; F Ghiringhelli; A Leroux; D Peiffert; C Borg; J F Bosset; G Créhange Journal: Oncoimmunology Date: 2017-11-27 Impact factor: 8.110