title: Immunological effects of bevacizumab-based treatment in metastatic colorectal cancer.
abstract: OBJECTIVE
  The efficacy of bevacizumab in metastatic colorectal cancer (mCRC) could be related not only to its well-known antiangiogenetic properties but also to a hypothetical effect on the immune system of the host.
  
  
  METHODS
  We enrolled mCRC patients treated with a bevacizumab-based first-line therapy. Lymphocyte and dendritic cell subsets were evaluated at baseline, 3rd and 6th cycle. The clinical efficacy was estimated as response rate and progression-free survival. Forty healthy subjects were used as reference.
  
  
  RESULTS
  Fifty-one patients were enrolled. In comparison with healthy subjects, they showed a decrease of T and B cell compartments. Bevacizumab ameliorated the impairment of lymphocyte subsets, especially for T cells. Responders showed a trend toward an increase of CD3 (p = 0.07) and CD4 (p = 0.05). Among patients with a progression-free survival >1 year, only CD19 (p = 0.033) and CD20 (p = 0.013) showed a significant increase. No baseline impairment and no significant modification of dendritic cells were found.
  
  
  CONCLUSIONS
  Bevacizumab-based therapy is able to increase B and T cell compartments. The expansion of T lymphocytes could imply an amelioration of dendritic cell-presenting capacity. These effects correlate with a more favourable clinical outcome and could be taken into account in clinical protocols aimed at combining antiangiogenetic-therapy with immunotherapy in mCRC.
authors.affiliation: Medical Oncology, Foundation IRCCS Policlinico S. Matteo, Pavia, Italy. m.manzoni@smatteo.pv.it
authors.forename: M
authors.initials: M
authors.lastname: Manzoni
authors.forename: B
authors.initials: B
authors.lastname: Rovati
authors.forename: M
authors.initials: M
authors.lastname: Ronzoni
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.forename: S
authors.initials: S
authors.lastname: Mariucci
authors.forename: V
authors.initials: V
authors.lastname: Ricci
authors.forename: E
authors.initials: E
authors.lastname: Gattoni
authors.forename: L
authors.initials: L
authors.lastname: Salvatore
authors.forename: C
authors.initials: C
authors.lastname: Tinelli
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: M
authors.initials: M
authors.lastname: Danova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000556:secondary; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab