title: Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.
abstract: BACKGROUND
  The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans.
  
  
  METHODS
  In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests.
  
  
  RESULTS
  We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control.
  
  
  CONCLUSIONS
  Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.
authors.affiliation: INSERM, UMR866, Dijon, France; Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Mignot
authors.affiliation: INSERM, UMR866, Dijon, France; Faculté de Médecine, Université de Bourgogne, Dijon, France; Service de Dermatologie, Centre Hospitalier Universitaire le Bocage, Dijon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Hervieu
authors.affiliation: Faculté de Médecine, Université de Bourgogne, Dijon, France; Service de Dermatologie, Centre Hospitalier Universitaire le Bocage, Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vabres
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire le Bocage, Dijon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dalac
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire le Bocage, Dijon, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Jeudy
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire le Bocage, Dijon, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Bel
authors.affiliation: INSERM, UMR866, Dijon, France; Faculté de Médecine, Université de Bourgogne, Dijon, France; Oncologie médicale, Centre Georges François Leclerc, Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: INSERM, UMR866, Dijon, France; Faculté de Médecine, Université de Bourgogne, Dijon, France; Oncologie médicale, Centre Georges François Leclerc, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014157:Transcription Factors; D003606:Dacarbazine