The P815 Mastocytoma Tumor Model

Abstract

This unit presents an experimental tumor model which has led to pivotal advances in tumor immunology culminating in the preclinical development of human cancer vaccines for melanoma. The model employs the use of the P815 mastocytoma cell line. Although the P815 cell line belongs to the mast cell lineage, it offers several advantages for in vivo experimentation of the tumor-host relationship. It grows progressively in the majority of syngeneic DBA/2 mice and can be implanted either intraperitoneally or subcutaneously. Moreover, immunogeneic variants have been created yielding tumors that are spontaneously rejected BB a behavior that has provided a context in which to study the immunologically relevant molecules and cells that dictate a successful anti-tumor response.

Reduced tumor‐antigen density leads to PD‐1/PD‐L1‐mediated impairment of partially exhausted CD8+ T cells

“…A TCR-transgenic model (2C TCR) [20] conditions, we observed the results analogous to the previously defined partial exhaustion state that occurs during chronic viral infections [17,22].…”

“…In order to resume chronic stimulation of antigen-specific T cells in vitro, we used a previously well-described model of repetitive stimulation [18][19][20]. This model was preferred as it allowed a standardized stimulation of CD8 1 T cells independently of PD-1 triggering and is known to yield T cells that are functionally very close to tumor-infiltrating lymphocytes found in melanoma tumors [6].…”

“…Repetitive stimulations of 2C TCR transgenic T cells using the P815.B71 cell line is a standard method that has been described previously to obtain T cells at different stages of activation [20]. In short, effector T cells were obtained by incubating 1 Â 10 5 purified naïve 2C T-cells with 5 Â 10 5 mitomycin C-treated P815.B7.1 for 5-7 days.…”

Antitumor T-cell responses contribute to the effects of dasatinib on c-KIT mutant murine mastocytoma and are potentiated by anti-OX40

“…P815 tumors elicit measurable T cell-mediated antitumor immunity, and 2 tumor antigens (P1A and P1E) in this model have been well characterized. 25,26 Dasatinib, a small molecule tyrosine kinase inhibitor approved by the Food and Drug Administration for the treatment of CML and Ph ϩ AML, has been shown to potently inhibit D814Y mutant c-KIT in P815 and a human mastocytoma cell line, inducing growth arrest and apoptosis of these tumor cells in vitro. [27][28][29] In addition to its effects on the D814Y mutant c-KIT, this drug has a very short biologic half-life (3-6 hours) 27 We consider the short half-life as an advantage for being combined with immuneboosting agents because most of the c-KIT tyrosine kinase inhibitors have been shown to negatively interfere with T-cell proliferation and function.…”

Behavior of the P1.HTR mastocytoma cell line implanted in the chorioallantoic membrane of chick embryos

“…The P1.HTR mastocytoma cell line, a highly transfectable variant of the P815 mastocytoma cell line, has been frequently used in tumor immunology studies in vitro (13) or in in vivo mouse models (11,14). Extensive studies have been performed concerning the influence of P1.HTR cells on cellular and humoral antitumor immune responses (15,16) but no effects on the host's vasculature have been described before.…”