Radiofrequency thermal ablation of breast tumors combined with intralesional administration of IL-7 and IL-15 augments anti-tumor immune responses and inhibits tumor development and metastasis.
Tumor development or recurrence is always a matter of concern following radiofrequency thermal ablation (RFA) of tumors. To determine whether combining RFA with immunologically active cytokines might induce tumor-specific immune responses against mammary carcinoma and inhibit tumor development or metastasis, we evaluated intralesional injection of IL-7 and IL-15 in RFA-treated murine tumors. We used two different breast carcinoma models: neu-overexpressing mouse mammary carcinoma (MMC) in FVBN202 transgenic mouse and 4T1 tumors in Balb/c mouse. MMC tend to relapse even in the presence of neu-specific immune responses, and 4T1 is a weakly immunogenic, aggressive and highly metastatic transplantable tumor. In vivo growth of both of these tumors is also associated with increased numbers of CD11b+Gr1+ myeloid-derived suppressor cells (MDSC). We showed for the first time that unlike RFA alone, RFA combined with the administration of intralesional IL-7 and IL-15 (after RFA), induced immune responses to tumors, inhibited tumor development and lung metastasis, and reduced MDSC.
Habibi
Mehran
M
Department of Microbiology and Immunology, VCU School of Medicine, Massey Cancer Center, 401 College Street, Box 980035, Richmond, VA 23298, USA.
Kmieciak
Maciej
M
Graham
Laura
L
Morales
Johanna K
JK
Bear
Harry D
HD
Manjili
Masoud H
MH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017115:Catheter Ablation / Q000379:methods; D005260:Female; D007107:Immune System; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000627:therapeutic use*; D015674:Mammary Neoplasms, Animal / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D051381:Rats
D000970:Antineoplastic Agents; D019409:Interleukin-15; D015851:Interleukin-7; D007371:Interferon-gamma