BACKGROUND: Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined. METHODS: TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed. RESULTS: Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25%, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration. CONCLUSIONS: A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.
BACKGROUND:Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined. METHODS: TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed. RESULTS: Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25%, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration. CONCLUSIONS: A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.
Authors: Paul A Antony; Ciriaco A Piccirillo; Akgül Akpinarli; Steven E Finkelstein; Paul J Speiss; Deborah R Surman; Douglas C Palmer; Chi-Chao Chan; Christopher A Klebanoff; Willem W Overwijk; Steven A Rosenberg; Nicholas P Restifo Journal: J Immunol Date: 2005-03-01 Impact factor: 5.422
Authors: Steven C Katz; Venu G Pillarisetty; Joshua I Bleier; T Peter Kingham; Umer I Chaudhry; Alaap B Shah; Ronald P DeMatteo Journal: Hepatology Date: 2005-08 Impact factor: 17.425
Authors: Julie R Brahmer; Scott S Tykodi; Laura Q M Chow; Wen-Jen Hwu; Suzanne L Topalian; Patrick Hwu; Charles G Drake; Luis H Camacho; John Kauh; Kunle Odunsi; Henry C Pitot; Omid Hamid; Shailender Bhatia; Renato Martins; Keith Eaton; Shuming Chen; Theresa M Salay; Suresh Alaparthy; Joseph F Grosso; Alan J Korman; Susan M Parker; Shruti Agrawal; Stacie M Goldberg; Drew M Pardoll; Ashok Gupta; Jon M Wigginton Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: Mary E Morgan; Jolanda H M van Bilsen; Aleida M Bakker; Bianca Heemskerk; Marco W Schilham; Franca C Hartgers; Berendina G Elferink; Linda van der Zanden; René R P de Vries; Tom W J Huizinga; Tom H M Ottenhoff; René E M Toes Journal: Hum Immunol Date: 2005-01 Impact factor: 2.850
Authors: Steven C Katz; John Hardaway; Ethan Prince; Prajna Guha; Marissa Cunetta; Ashley Moody; Li Juan Wang; Vincent Armenio; N Joseph Espat; Richard P Junghans Journal: Cancer Gene Ther Date: 2019-06-03 Impact factor: 5.987
Authors: Michael J Cavnar; Simon Turcotte; Steven C Katz; Deborah Kuk; Mithat Gönen; Jinru Shia; Peter J Allen; Vinod P Balachandran; Michael I D'Angelica; T Peter Kingham; William R Jarnagin; Ronald P DeMatteo Journal: Ann Surg Oncol Date: 2017-02-17 Impact factor: 5.344
Authors: Rachel A Burga; Mitchell Thorn; Gary R Point; Prajna Guha; Cang T Nguyen; Lauren A Licata; Ronald P DeMatteo; Alfred Ayala; N Joseph Espat; Richard P Junghans; Steven C Katz Journal: Cancer Immunol Immunother Date: 2015-04-08 Impact factor: 6.968
Authors: Steven C Katz; Rachel A Burga; Elise McCormack; Li Juan Wang; Wesley Mooring; Gary R Point; Pranay D Khare; Mitchell Thorn; Qiangzhong Ma; Brian F Stainken; Earle O Assanah; Robin Davies; N Joseph Espat; Richard P Junghans Journal: Clin Cancer Res Date: 2015-04-07 Impact factor: 12.531