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Induction of new antigenic properties on DTIC-treated L1210 clones
1Department of Pharmacology, School of Medicine, Università di Milano, Italia.
Abstract:
In vivo treatment of mouse leukemia L1210 with DTIC can induce new antigens on tumor cells that are not detectable on parental cells and that are transmissible as a genetic character. Moreover, L1210/DTIC is rejected by syngeneic hosts. The aim of this study was to investigate whether DTIC selects pre-existing immunogenic clones rather than inducing ex novo new antigenic determinants and to verify the number of induced antigens. L1210 leukemia was cloned in vitro and 4 clones were treated in vivo with DTIC. All the treated clones displayed antigenic properties since they were rejected by syngeneic hosts. Cytotoxic T lymphocytes (CTL) activated against one DTIC clone could recognize and lyse the relevant target. One of these DTIC-modified clones (L4/DTIC) was recloned and the subclones were tested in vivo and in vitro. Two out of six subclones were rejected by syngeneic hosts. CTL specific against these two clones were able to recognize and lyse all the other clones to different degrees. The degree of susceptibility to lysis did not correlate with the capability to evoke an immune response in vivo. Based on these findings we conclude that DTIC does not select pre-existing clones but modifies the tumor cells antigenically, and that the antigenicity induced by DTIC in a cloned tumor line is due to the presence of common antigens shared to different degrees with treated cells.
Insights
Dacarbazine (DTIC) treatment of mouse leukemia L1210 does not select pre-existing tumor cell clones. Instead, DTIC modifies tumor cells, inducing new antigens that trigger an immune response.
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Dacarbazine (DTIC) treatment of mouse leukemia L1210 induces new antigens on tumor cells.
- These induced antigens are genetically transmissible and lead to tumor rejection by syngeneic hosts.
- The mechanism by which DTIC induces antigenicity remains unclear, with debate on whether it selects pre-existing clones or induces new antigenic determinants.
Purpose of the Study:
- To investigate whether DTIC selects pre-existing immunogenic clones or induces new antigenic determinants.
- To determine the number of antigens induced by DTIC treatment.
- To characterize the antigenic properties of DTIC-modified tumor cells and their interaction with the immune system.
Main Methods:
- Cloning of L1210 leukemia cell line in vitro.
- In vivo treatment of cloned leukemia cells with DTIC.
- Testing the immunogenicity of DTIC-treated clones through rejection by syngeneic hosts.
- Activation and testing of cytotoxic T lymphocytes (CTLs) against DTIC-modified clones.
- Recloning of a DTIC-modified subline (L4/DTIC) and characterization of its subclones.
Main Results:
- All DTIC-treated clones exhibited new antigenic properties, leading to rejection by syngeneic hosts.
- Cytotoxic T lymphocytes (CTLs) activated against one DTIC-modified clone could recognize and lyse relevant target cells.
- Recloning of a DTIC-modified clone (L4/DTIC) revealed that two out of six subclones were rejected by hosts.
- CTLs specific for these rejected subclones could lyse other DTIC-modified clones to varying degrees.
- The degree of susceptibility to CTL lysis did not correlate with the in vivo immune response capability.
Conclusions:
- DTIC treatment antigenically modifies tumor cells rather than selecting pre-existing immunogenic clones.
- The induced antigenicity in cloned tumor lines is attributed to common antigens shared among treated cells.
- DTIC induces a consistent antigenic modification across a cloned tumor line, leading to immune recognition.