Related Experiment Videos
Nitric oxide-independent CTL suppression during tumor progression: association with arginase-producing (M2) myeloid
Yuanqing Liu1, Jo A Van Ginderachter, Lea Brys
1Department of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Belgium. tmliuyua@vub.ac.be
Abstract:
Most of the mice bearing a s.c. BW-Sp3 lymphoma tumor mount a CD8(+) T cell-mediated response resulting in tumor regression. Nonetheless, tumor progression occurs in some of the recipients and is associated with CTL inactivity. We demonstrated that T cell-activating APC were induced in regressors whereas T cell suppressive myeloid cells predominated in the spleen of progressors. Indeed, in vitro depletion of either the adherent or the CD11b(+) populations restored T cell cytotoxicity and proliferation in these mice. This CTL inhibition was cell-to-cell contact-dependent but not mediated by NO. However, the same progressor suppressive cells prevented the activity of in vitro-restimulated CTLs derived from regressors in a cell-to-cell contact and NO-dependent fashion. Thus, either the NO-dependent or -independent suppressive pathway prevailed, depending on the target CTL population. In addition, the suppressive population expressed a high arginase activity, suggesting an association of the suppressive phenotype with alternatively activated (M2) myeloid cells. However, the high arginase activity is not directly involved in the suppressive process. Our results provide new insights for myeloid cell-mediated CTL inhibition during cancer progression.
Insights
Tumor progression in mice is linked to suppressive myeloid cells that inhibit CD8(+) T cell activity. These myeloid cells use cell contact and nitric oxide (NO) dependent pathways to impair T cell responses, offering insights into cancer immune evasion.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- CD8(+) T cell-mediated responses are crucial for tumor regression in many cancers.
- Tumor progression can occur despite initial anti-tumor immunity, often associated with immune suppression.
- Myeloid cells play a complex role in cancer immunity, capable of both promoting and suppressing anti-tumor responses.
Purpose of the Study:
- To investigate the mechanisms by which tumor progression occurs in the presence of anti-tumor T cell responses.
- To identify the role of myeloid cells in mediating T cell inactivity during cancer progression.
- To elucidate the specific pathways involved in myeloid cell-induced T cell suppression.
Main Methods:
- Analysis of myeloid cell populations in the spleen of mice with regressing versus progressing tumors.
- In vitro depletion of specific myeloid cell populations to assess their impact on T cell function.
- Investigating the role of cell-to-cell contact and nitric oxide (NO) in T cell suppression.
- Assessing arginase activity in suppressive myeloid cells.
Main Results:
- Progressor mice, unlike regressors, exhibit a predominance of T cell suppressive myeloid cells in their spleen.
- Depletion of adherent or CD11b(+) myeloid cells restores T cell cytotoxicity and proliferation in progressors.
- Myeloid cell-mediated CTL inhibition is dependent on cell-to-cell contact and can be NO-dependent or independent, varying with the target T cell population.
- Suppressive myeloid cells show high arginase activity, suggesting a link to alternatively activated (M2) myeloid cells, though arginase itself is not directly involved in suppression.
Conclusions:
- Myeloid cell-mediated suppression of CD8(+) T cells is a key mechanism contributing to tumor progression.
- Distinct suppressive pathways, involving cell contact and NO, are employed by myeloid cells to inhibit T cell activity.
- These findings highlight the critical role of myeloid cell immunomodulation in overcoming anti-tumor immunity and suggest potential therapeutic targets for enhancing cancer immunotherapy.