Infiltration of immune competent cells into primary tumors and their surrounding connective tissues in mice

Background: Due to the fact that a close physical contact between NK- and T-cells and cancer cells themselves is necessary to kill cancer cells, we wanted to study the distribution of immunocompetent cells in syngeneic and xenograft tumor models with immunodeficiency of the specific (T- and B-cells) immune system. Because of this approach we focused on the cells of the innate immune system. Methods: Paraffin wax embedded primary breast cancers from the syngeneic mouse WAP-T model and from xenografted tumors of breast, colon, melanoma, ovarian, neuroblastoma, pancreatic, prostate and small cell lung cancer were investigated for the infiltration of immunocompetent cells. The percentage of the labelled cells was semiquantitatively recorded and attributed to the following locations: adjacent adipose tissue, the tumor capsule, the intra-tumoral septae and the malignant cells themselves. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a marker for dendritic cells, CD11b as a marker for NK cells and CD68 for macrophages. Results: Xenograft tumors: in relation to the localisation of CD45, CD11b positive, NK and dendritic cells, the highest score was found in the adjacent adipose tissue, followed by lesser infiltration in the malignant tissue. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast, small cell lung cancer and in neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer and strongest in prostate and pancreatic cancer.Syngeneic tumors: the highest score of CD45, CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser degree of infiltration of the cancer tissue itself.Conclusions: Our findings show in several neoplastic entities that the majority of immune competent cells are not directly located at the malignant cells but are present in the surrounding tumor stroma and connective tissue capsule. Hence the tumor stroma represents a considerable barrier for lymphocytes to come in direct contact with the malignant cells. Therefore strategies should be employed to make the tumor stroma more penetrable for immune cells in order to increase their efficacy.