title: Tumor infiltration by T lymphocytes expressing chemokine receptor 7 (CCR7) is predictive of favorable outcome in patients with advanced colorectal carcinoma.
abstract: OBJECTIVE
  An efficient adaptive immunity is critical for a longer survival in cancer. We investigated the prognostic value of tumor infiltration by CD8(+) T cells expressing the chemokine-receptor-7 (T(ccr7)) and the correlation between tumor infiltration by T(ccr7) and regulatory CD4(+)FoxP3(+) T cells (T(reg)) in 76 metastatic colorectal cancer (mCRC) patients enrolled in a phase III trial.
  
  
  METHODS
  T(ccr7) and T(reg) cell infiltration in tumor samples was quantified by immunohistochemistry. The correlation among T(ccr7), T(reg) tumor infiltration, and patients' outcome was evaluated.
  
  
  RESULTS
  High T(ccr7) tumor infiltration was predictive of prolonged OS [high vs. low T(ccr7) score: median 38 months (95% CI: 24.5-51.4) vs. 20 months (95% CI: 11.4-28.5); HR = 0.48 (95% CI: 0.24-0.96); P = 0.03] and prolonged progression-free survival [PFS; high vs. low T(ccr7) score: median 12 months (95% CI: 7.7-16.2) vs. 7 months (95% CI: 5.2-8.7); HR = 0.54 (95% CI: 0.28-1.01); P = 0.01] after front-line chemotherapy. Regression analysis did not show correlation between T(ccr7) and T(reg) infiltration levels. However, the cluster of patients showing concomitant high infiltration by both T(ccr7) and T(reg) disclosed a favorable outcome [double high vs. double low tumor infiltration score: median OS = 35 months (95% CI: 20.8-49.1) vs. 17 months (95% CI: 4.6-29.3); HR = 0.32 (95% CI: 0.12-0.87); P = 0.02 and median PFS = 11 months (95% CI: 9.4-12.5) vs. 5 months (95% CI: 2.2-7.7); HR = 0.43 (95% CI: 0.17-1.06); P = 0.01].
  
  
  CONCLUSIONS
  High T(ccr7) tumor infiltration score is a favorable prognostic factor for mCRC. Our findings underline the relevance of microenvironment-related immunologic events for patient outcome.
authors.affiliation: Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Rotundo
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Del Vecchio
authors.forename: Chiara
authors.initials: C
authors.lastname: Ginanneschi
authors.forename: Antonella
authors.initials: A
authors.lastname: Licchetta
authors.forename: Raffaele
authors.initials: R
authors.lastname: Conca
authors.forename: Serena
authors.initials: S
authors.lastname: Apollinari
authors.forename: Fabio
authors.initials: F
authors.lastname: De Luca
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7