Background Tumor immunogenicity is a critical factor responsible for the limited success of cancer immunotherapy and determine the need for personalized treatment. Correct evaluation of effectiveness of cancer treatments and their combination is inseparable from the proper selection of the experimental tumor model. The lack of knowledge about the immunogenicity of animal tumor models makes it difficult to evaluate the efficacy of cancer immunotherapy and becomes the reason why the results of experimental studies are not suitable for biomedical research. The goal of our work was to evaluate the immunogenic properties of two murine cancer models - Lewis lung carcinoma LLC1 and glioma GL261 and to select two immunologically different tumor models for further chemo-immunotherapy research.
Materials and Methods Firstly, the immunological properties of GL261 and LLC1 cells were assessed in vitro. For this reason, expression of MHC I, PD-L1 and CD44 on LLC1 and GL261 cells surface was evaluated. Then the ability of GL261 and LLC1 lysates to activate immature murine dendritic cells (DCs) was estimated. Murine DCs were generated from bone marrow cells by cultivating them with GM-CSF for 6 days1 and then maturing them for 24 hours with LLC1 and GL261 lysate supplemented with E. coli lipopolysaccharide. Activation status of DCs was assessed by the expression of surface markers CD11c, MHC II, CD80, CD86, CD40 and CCR7. Later C57BL/6 mice were inoculated s.c. into the left side of the back with GL261 or LLC1 cells. Tumor develpoment was monitored every 2–3 days and then tumors reached a size of ~1.5 cm3 mice were sacrificed. Tumors were collected for evaluation of immune cell infiltration and predominant cytokine profile. Also inactivated GL261 and LLC1 cells were inoculated prophylactically before tumor inoculation and their ability to induce antitumor immune memory was investigated.
Results Our study revealed different immunogenic properties of LLC1 and GL261 cells. LLC1 tumors developed significantly faster than GL261 tumors. Infiltration of immune cells, especially CD8+ lymphocytes and NK cells, was more prominent in GL261 than in LLC1 tumors. Also MHC I and PD-L1 expression was significantly higher on GL261 cells. They also showed better ability to induce antitumor immune memory and to activate murine dendritic cells. Cytokine profile analysis further confirmed immunological differences between LLC1 and GL261 cells.
Conclusions LLC1 and GL261 tumors possess different immunogenic properties - GL261 tumor reflects immunogenic tumor model while LLC1 tumor - nonimmunogenic model. These results confirm us the idea that the immune subtype of tumour should be taken into account when evaluating the results of variuos combinations of chemo-immunotherapies.
Lutz MB, et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999 Feb 1;223(1):77–92.
Disclosure Information K. Zilionyte: None. A. Mlynska: None. V. Pasukoniene: None.
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