title: Recruitment of host CD8+ T cells by tumor-infiltrating lymphocytes and recombinant interleukin-2 during adoptive immunotherapy of cancer.
abstract: BACKGROUND
  Previously we demonstrated that optimal doses of tumor-infiltrating lymphocytes (TIL) concomitant with recombinant interleukin-2 (rIL-2) effectively mediated complete tumor regression of murine 3-day pulmonary metastases.
  
  
  METHODS
  In the present study we have investigated the contribution of the host immune response to the effectiveness of adoptive immunotherapy with TIL in combination with low-dose rIL-2. All experiments were performed in a murine pulmonary metastases model induced by intravenous injection of methylcholanthrene-induced sarcoma (MCA-105) cells into C57BL/6 mice. As a novel approach we used monoclonal antibody specific for CD4+ or CD8+ T cells to deplete the host of its T-cell subpopulations.
  
  
  RESULTS
  Depletion of host CD8+ T cells 24 hours after tumor injection and 48 hours before TIL+rIL-2 treatment abrogated all antitumor activity of this type of immunotherapy and resulted in significant metastatic pulmonary disease (p < 0.001). In contrast, depletion of host CD4+ T cells did not alter the efficacy of TIL+rIL-2 treatment in tumor eradication. The loss of tumoricidal activity of TIL+rIL-2 treatment in a CD8+ T cell-depleted host could be overcome by adding back normal uneducated splenocytes 2 hours after TIL therapy (p < 0.001). In contrast, adding back CD8- CD4+ splenocytes to a CD8+ T cell-depleted host 2 hours after TIL+rIL-2 treatment resulted in significant pulmonary disease comparable to untreated animals.
  
  
  CONCLUSIONS
  We conclude that the recruitment of host CD8+ T cells by adoptively transferred TIL+rIL-2 appears to be important for effective tumor eradication in this type of immunotherapy.
authors.affiliation: Department of Surgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: U L
authors.initials: UL
authors.lastname: Burger
authors.forename: M P
authors.initials: MP
authors.lastname: Chang
authors.forename: P S
authors.initials: PS
authors.lastname: Goedegebuure
authors.forename: T J
authors.initials: TJ
authors.lastname: Eberlein
authors.forename: S
authors.initials: S
authors.lastname: Adams-Hodgins
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000628:therapy*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins