Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

• Published in: PloS one 2016-07, Vol.11 (7), p.e0159515-e0159515
• Main Authors: Habets, Thomas H P M, Oth, Tammy, Houben, Ans W, Huijskens, Mirelle J A J, Senden-Gijsbers, Birgit L M G, Schnijderberg, Melanie C A, Brans, Boudewijn, Dubois, Ludwig J, Lambin, Philippe, De Saint-Hubert, Marijke, Germeraad, Wilfred T V, Tilanus, Marcel G J, Mottaghy, Felix M, Bos, Gerard M J, Vanderlocht, Joris
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies; Antibodies, Monoclonal - biosynthesis; Antibody response; Antigens; Bearing; Biology and Life Sciences; Cancer; Cancer treatment; Carcinoma; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - radiotherapy; Cytometry; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Developmental biology; Dose Fractionation; Female; Flow cytometry; Gamma Rays - therapeutic use; Granulocytes; Health aspects; Hematology; Immune response; Immune response (humoral); Immune system; Immunity, Humoral; Immunoglobulin Isotypes - blood; Immunoglobulins; Immunology; Immunotherapy; Internal medicine; Isotypes; Laboratory animals; Ligands; Lymphocytes; Lymphocytes T; Mammary gland; Mammary Glands, Animal - immunology; Mammary Glands, Animal - pathology; Mammary Glands, Animal - radiation effects; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - radiotherapy; Medicine and Health Sciences; Membrane Proteins - pharmacology; Metastasis; Methods; Mice; Mice, Inbred BALB C; Nuclear medicine; Oncology; Radiation therapy; Radiotherapy; Regression; Research and Analysis Methods; Stimulation; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159515

Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects.