INDUCING ANTI-TUMORAL RESPONSE BY ACTIVATION OF INNATE IMMUNE CELLS IN THE TUMOR MICROENVIRONMENT

Ehud Shahar ¹ Raphael Gorodetsky ² Elina Aizenshtein ¹ Jacob Pitcovski ¹

¹Department of Vaccine Development, Migal - Galilee Research Institute, Kiryat Shmona
²Department of biotechnology and radiobiology, Sharett Institute of Oncology, Hadassah Hebrew-University Medical Center, Jerusalem

Tumor microenvironment (TMI) consists of multitude immune cells which can comprise up to 50% of the tumor mass. The most abundant cells in the TMI often are tumor associated macrophages (TAM) and tumor associated neutrophils (TAN). These cells may potentially express anti-tumoral cytotoxic effect, and have the potential to induce a broad range of cellular immune responses. However, in the developing tumor, due to substances secreted by the tumor cells, TAM and TAN are converted to act in a pro-tumor manner. The purpose of this study was the optimization and characterization of a treatment aimed at inducing an anti-tumoral response of innate immune cells in the TMI. In a melanoma B16 mice model, tumors were harvested and analyzed for immune cells populations. Micro-particles carrying targeting and induction components were injected intra-tumorally and the responses of the tumors were monitored. Without treatment the CD45⁺ cells ratio of total TMI decreased as tumor progressed. Particles carrying Toll-like receptor ligands inhibited tumor growth, inducing significant elevation of CD45⁺ cells in the TMI. Using different inducing molecules (inducers) or simultaneous use of several inducers enabled the stimulation of specific immune cell populations within the tumor. The current study suggests that by using tumor targeted particles with adequate inducers, one could change the tumor microenvironment innate immune cells toward an anti-tumor response.