Abstract
To fight cancer more efficiently with cell-based immunotherapy, more information about the cells of the immune system and their interaction with cancer cells in vivo is needed. Therefore 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 by immunohistochemistry using antibodies against leukocyte markers. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a dendritic cell marker, CD11b as an NK cell marker, and CD68 as a marker for macrophages. The labeled immune cells were attributed to the following locations: adjacent adipose tissue, tumor capsule, intra-tumoral septae, and cancer cells directly. In xenograft tumors, the highest score of CD45 and CD11b positive, NK, and dendritic cells were found in the adjacent adipose tissue, followed by lesser infiltration directly located at the cancer cells themselves. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast cancer, small cell lung cancer, neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer, strongest infiltration in prostate and pancreatic cancer. In the syngeneic tumors, the highest score of CD45 and CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser infiltration of the cancer tissue. Our findings argue for paying more attention to investigate how immune-competent cells can reach the tumor cells directly.
Highlights
Cancer remains a considerable health care challenge, with the lifetime risk of getting cancer being 43% for women and 51% for men in Germany (Kobold et al, 2015) [1].So far, cancer therapy has been based on surgery, radiotherapy, and/or chemotherapy.the landscape of cancer therapy is probably changing dramatically with the advent of new immune therapeutic agents
The present study focuses on cells of the innate immune system to fill the existing knowledge gap concerning dendritic cells, monocytes/macrophages, and NK cells in xenograft and syngeneic mouse models
Breast Cancer In T47D primary tumors, 70% of dendritic cells, no CD45 positive cells, 5% of CD11b positive cells, and no CD68 positive cells were found in the adjacent adipose tissue
Summary
Cancer remains a considerable health care challenge, with the lifetime risk of getting cancer being 43% for women and 51% for men in Germany (Kobold et al, 2015) [1].So far, cancer therapy has been based on surgery, radiotherapy, and/or chemotherapy.the landscape of cancer therapy is probably changing dramatically with the advent of new immune therapeutic agents. Immunotherapy attracted much attention as in some cancers, most of the cells making up the tumor mass have been classified as leukocytes (Allavena et al 2008, Colotta et al 2009, Sica et al.2008) [2,3,4] Despite this immune cell infiltration, tumor cells are not efficiently attacked as they continue to grow. Marquez-Rodas et al (Marquez-Rodas et al, 2015) [5] and Postow et al (Postow et al, 2015) [6] described that tumor cells were able to block the attachment of antigen-presenting leukocytes to T lymphocytes, stopping their attack capacity by so-called checkpoint mechanisms. These include the blockade of the receptorligand-interaction between cytotoxic T lymphocyte antigen-4 (CTLA-4) and CD80/CD86 or between programmed death-1 protein (PD-1) and its ligand (Deppert and Bruns, 2016, Hamid et al, 2011, Krummel and Allison, 1996) [7,8,9]
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