CCL21 induces extensive intratumoral immune cell infiltration and specific anti-tumor cellular immunity.
Chemokines are vital messengers that regulate immune cell activity. The chemokine CCL21 is normally expressed in secondary lymphoid organs and acts as a chemoattractant for several populations of immune cells. Herein, we report that intratumoral CCL21 administration recruited significant numbers of immune cells into murine pancreatic tumors and inhibited tumor growth. Detailed flow cytometric and confocal analysis of CCL21-treated tumor cell isolates revealed increased lymphoid-related dendritic cells (lDC) and myeloid DC (mDC), naïve and mature T cells, natural killer (NK) cells, and NKT cells infiltrating the tumor mass. Furthermore, CCL21 intratumoral treatments resulted in significant tumor growth inhibition in wild-type (WT) C57BL/6 mice, but no therapeutic benefit was observed in C57BL/6 RAG2-/-Pfp-/- mice, suggesting that the growth inhibition observed was immunologically mediated. CCL21 intratumoral injections generated immune responses that were tumor-specific and that could be transferred to naïve animals via splenocytes. In addition, intratumoral injection of CCL21 into pancreatic tumors reduced the growth of distant tumors as well as treated tumors. Thus, these data demonstrate in a pancreatic tumor model that intratumoral administration of CCL21 can cause significant immune cell infiltration of the tumor mass, delay growth of treated tumors, and generate a tumor-specific cellular immune response.
Turnquist
Heth R
HR
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Lin
Xuede
X
Ashour
Abdelkader E
AE
Hollingsworth
Michael A
MA
Singh
Rakesh K
RK
Talmadge
James E
JE
Solheim
Joyce C
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D007107:Immune System / Q000473:pathology; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy; D011379:Prognosis; D013154:Spleen / Q000166:cytology
D000970:Antineoplastic Agents; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC