PURPOSE: The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer-TNM (AJCC/UICC-TNM) staging system. PATIENTS AND METHODS: We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. RESULTS: Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8(+) cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival. CONCLUSION: Assessment of CD8(+) cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
PURPOSE: The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer-TNM (AJCC/UICC-TNM) staging system. PATIENTS AND METHODS: We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. RESULTS: Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8(+) cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival. CONCLUSION: Assessment of CD8(+) cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
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: Jeffrey Chou; Lilien N Voong; Christie L Mortales; Andrea M H Towlerton; Seth M Pollack; Xiaoji Chen; Cassian Yee; Paul F Robbins; Edus H Warren Journal: J Immunother Date: 2012 Feb-Mar Impact factor: 4.456
Authors: Shawn M Jensen; Christopher G Twitty; Levi D Maston; Paul A Antony; May Lim; Hong-Ming Hu; Ulf Petrausch; Nicholas P Restifo; Bernard A Fox Journal: J Immunol Date: 2012-06-20 Impact factor: 5.422
Authors: Johannes A Veit; Daniela Heine; Julia Thierauf; Jochen Lennerz; Subasch Shetty; Patrick J Schuler; Theresa Whiteside; Dirk Beutner; Moritz Meyer; Inga Grünewald; Gerd Ritter; Sacha Gnjatic; Andrew G Sikora; Thomas K Hoffmann; Simon Laban Journal: Head Neck Date: 2016-02-13 Impact factor: 3.147
Authors: Jessie L-S Au; Bertrand Z Yeung; Michael G Wientjes; Ze Lu; M Guillaume Wientjes Journal: Adv Drug Deliv Rev Date: 2015-12-11 Impact factor: 15.470
Authors: Lauren V Wood; Antonio Fojo; Brenda D Roberson; Meghan S B Hughes; William Dahut; James L Gulley; Ravi A Madan; Philip M Arlen; Marianna Sabatino; David F Stroncek; Luciano Castiello; Jane B Trepel; Min-Jung Lee; Howard L Parnes; Seth M Steinberg; Masaki Terabe; Julia Wilkerson; Ira Pastan; Jay A Berzofsky Journal: Oncoimmunology Date: 2016-07-01 Impact factor: 8.110
Authors: Ilaria Marigo; Serena Zilio; Giacomo Desantis; Bernhard Mlecnik; Andrielly H R Agnellini; Stefano Ugel; Maria Stella Sasso; Joseph E Qualls; Franz Kratochvill; Paola Zanovello; Barbara Molon; Carola H Ries; Valeria Runza; Sabine Hoves; Amélie M Bilocq; Gabriela Bindea; Emilia M C Mazza; Silvio Bicciato; Jérôme Galon; Peter J Murray; Vincenzo Bronte Journal: Cancer Cell Date: 2016-09-12 Impact factor: 31.743