Immune rejection of intracerebral gliomas using lymphocytes from glioma-bearing rats

Area of Science:

• Immunology
• Oncology
• Neuroscience

Background:

• Naturally occurring malignancies often evade immune detection.
• The mechanisms behind this immune evasion, whether antigen presentation defects or immune suppression, remain unclear.

Purpose of the Study:

• To investigate if progressing intracerebral malignancies impair the production of peripheral autologous glioma antigen-specific immune responses.
• To determine the cause of reduced anti-tumor immunity in cancer-bearing hosts.

Main Methods:

• Peripheral immunization of glioma-bearing and non-glioma-bearing animals with cancer cells and adjuvant.
• Assessing glioma antigen-specific cytotoxic T lymphocyte activity.
• Evaluating the in vivo efficacy of immune cell populations in rejecting intracerebral tumors.
• Implementing in vivo and in vitro manipulations to reduce immune suppression.

Main Results:

• Both glioma-bearing and non-glioma-bearing animals produced similar levels of glioma antigen-specific cytotoxic T lymphocyte activity upon peripheral immunization.
• Immune cell populations from glioma bearers were significantly less effective at rejecting intracerebral tumors compared to non-cancer bearers.
• Manipulations to reduce nonspecific immune suppression did not improve the in vivo efficacy of T-lymphocyte populations.
• The presence of tumors appeared to augment, not suppress, cancer antigen-specific responses.

Conclusions:

• Reduced anti-tumor efficacy in glioma bearers is likely due to clonal anergy or deletion of immune effector cells, rather than generalized immune suppression.
• Despite decreased in vivo efficacy, immune effector cells capable of rejecting intracerebral malignancy can be generated from cancerous hosts.