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Published on: June 12, 2021
Deficiency in immunocompetence of mice cured from large MOPC-315 plasmacytomas by melphalan therapy
S Shoval1, R Ophir, S Ben-Efraim
1Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Israel.
Abstract:
Mice cured from large MOPC-315 tumors by a single dose of melphalan, 7.5 mg/kg, were examined for up to 60 days after the drug treatment (71 days after the tumor inoculation) for their ability to respond to mitogenic stimulation, specific and nonspecific antigenic stimulation and for their susceptibility to inoculation with an unrelated tumor, L10 lymphoma. The response of spleen cells from cured mice to mitogenic stimulation by phytohemagglutinin or concanavalin A was slightly depressed at an early stage after the drug treatment. The allogeneic response against C57BL spleen cells and the antibody response against sheep red blood cells (SRBC) of spleen cells from cured mice remained below normal levels during the whole observation period. The deficiency in response to antigenic stimulation was found to be due to impairment in T-cell function. Cured mice were also deficient in their response to SRBC immunization (antibody and delayed-type hypersensitivity responses) and were more susceptible to inoculation with an unrelated tumor, L10 lymphoma, than normal, noninoculated mice. On the other hand, spleen cells of cured mice developed a highly specific cytotoxic response against target MOPC-315 tumor cells and the cured mice were resistant to challenge with an otherwise highly tumorigenic dose of MOPC-315. Thus, cured mice remained deficient for a long period of time in their response to MOPC-315-unrelated antigens but, at the same time, they showed a potent specific antitumor immunity potential in vivo and in vitro.
Insights
Melphalan treatment cured MOPC-315 tumors in mice but impaired T-cell function, leading to reduced responses to unrelated antigens. However, specific immunity against the MOPC-315 tumor remained potent.
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Melphalan is a chemotherapy drug used to treat various cancers.
- Understanding the long-term immunological effects of chemotherapy is crucial for cancer survivors.
- The MOPC-315 tumor model in mice provides a system to study tumor immunity and drug effects.
Purpose of the Study:
- To evaluate the long-term immune status of mice cured from MOPC-315 tumors using melphalan.
- To assess the impact of melphalan treatment on T-cell function and immune responses to both specific and unrelated antigens.
- To determine the susceptibility of cured mice to unrelated tumor challenges.
Main Methods:
- Mice bearing MOPC-315 tumors were treated with a single dose of melphalan (7.5 mg/kg).
- Immune responses were assessed up to 60 days post-treatment, including mitogenic stimulation, allogeneic responses, antibody production to sheep red blood cells (SRBC), and delayed-type hypersensitivity.
- Tumor susceptibility was tested using an unrelated tumor (L10 lymphoma) and challenge with MOPC-315.
Main Results:
- Melphalan treatment led to a persistent deficiency in T-cell function and reduced responses to unrelated antigens (SRBC, allogeneic cells).
- Cured mice showed increased susceptibility to L10 lymphoma challenge.
- Despite immune deficiencies, cured mice developed specific cytotoxic responses against MOPC-315 tumor cells and were resistant to MOPC-315 re-challenge.
Conclusions:
- Melphalan-induced tumor cure in mice results in long-lasting T-cell dysfunction and impaired immunity to unrelated antigens.
- This immune impairment can increase susceptibility to secondary tumor challenges.
- Crucially, specific antitumor immunity against the original MOPC-315 tumor is maintained or even enhanced post-treatment.

