Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma

Blood. 2015 Jan 1;125(1):82-9. doi: 10.1182/blood-2014-07-592162. Epub 2014 Oct 7.


Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at as #NCT01926639.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • CD8-Positive T-Lymphocytes / cytology
  • Cancer Vaccines / therapeutic use
  • Dendritic Cells / drug effects
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Lymph Nodes / pathology*
  • Lymphoma, Follicular / therapy*
  • Middle Aged
  • Pilot Projects
  • Positron-Emission Tomography
  • Recurrence
  • Remission Induction
  • Rituximab
  • Skin Neoplasms / therapy
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Antibodies, Monoclonal, Murine-Derived
  • Cancer Vaccines
  • Rituximab
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data