Distinct innate immune responses to different murine mammary carcinoma are evident within the first 72 hours of tumor injection

Abstract

Abstract We used three different murine mammary carcinoma, each syngeneic in Balb/c mice, to study the early anti-tumor immune response. Initial analysis showed that the number of cells at the tumor sites almost doubled between 12–72 hours going from about 3e5 cells at 12 hours to about 6e5 cells at 72 hours. Surface staining revealed that the immune response during this time period was predominated by Gr1+ and F4/80+ cells. Strikingly, similar cell numbers and cell types were recruited to saline injected sites suggesting that these cells may be recruited non-specifically. However, closer examination revealed significant differences not only between the saline and tumor injected sites, but also among different tumor sites. For instance, at 12 hours post injection there were significantly more Gr1+ cells at the EMT6 tumor site than at the 4T1 tumor site, and at 48 hours there were significantly more Gr1+ cells at the 168 tumor site than at the saline and 4T1 tumor sites. At 24 hours post injection there were significantly more F4/80+ cells at the EMT6 tumor site than at the 4T1, 168 and saline injected sites, and at 72 hours post injection there were significantly more F4/80+ cells at the EMT6 tumor site compared to the 4T1 and 168 tumor sites. Next, we collected the Gr1+ and F4/80+ cells from the sites 24 hours after tumor delivery and using qRT-PCR we found several additional differences. For instance, the Gr1+ cells from the EMT6 tumor site expressed more arginase and less CCL2 than the Gr1+ cells from the 4T1 and 168 tumor sites, and the F4/80+ cells from the EMT6 site expressed more MMP-9 and TNF-a than F4/80+ cells from the 4T1 and 168 tumor sites. Collectively, these data indicated that a unique anti-tumor immune response was evident within hours of tumor delivery.