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Functional OCT4-specific CD4+ and CD8+ T cells in healthy controls and ovarian cancer patients
Jiabo Di1, Leon F A G Massuger, Tjitske Duiveman-de Boer
1Department of Tumor Immunology; Nijmegen Centre for Molecular Life Sciences; Radboud University Nijmegen Medical Centre; Nijmegen, The Netherlands.
Abstract:
The identification of growth and differentiation pathways that are responsible for the proliferation and survival of cancer stem cells (CSCs) has opened avenues for the discovery of novel therapeutic targets. In the initial phase of an anticancer immune response, T cells specific for tumor-associated antigens develop in patients and, at least under selected circumstances, are able to eliminate malignant cells. However, it remains unknown whether CSC-specific T cells are also operational. We found naturally occurring multifunctional CD4+ and CD8+ T cells specific for the stem cell marker OCT4 among the peripheral blood mononuclear cells (PBMCs) of both healthy individuals and ovarian cancer patients. Moreover, lymphocytes isolated from the ascites of patients affected by ovarian malignancies also contained OCT4-specific T cells. OCT4-reactive CD4+ T cells did not produce interferon γ (IFNγ) and IFNγ-inducible protein 10 (IP-10) but were capable of proliferation upon stimulation with dendritic cells (DCs) loaded with an OCT4-derived peptide or OCT4 mRNA. OCT4-reactive CD8+ cells did not proliferate in response to a similar challenge, yet produced IP-10 as well as sufficient amounts of IFNγ to induce IP-10 . Furthermore, CD8+ cytotoxic T cells were able to release their lysosomal components, as indicated by the mobilization of CD107a. These results demonstrate the existence of anti-CSC specific T cells in ovarian cancer patients.
Insights
Researchers found T cells targeting cancer stem cells (CSCs) in ovarian cancer patients. These OCT4-specific T cells, including CD4+ and CD8+ types, show potential for new anti-cancer therapies.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Cancer stem cells (CSCs) drive tumor growth and survival, representing key therapeutic targets.
- Anticancer immune responses involve T cells recognizing tumor antigens, but their role against CSCs is unclear.
Purpose of the Study:
- To investigate the presence and function of T cells specific for cancer stem cells (CSCs) in ovarian cancer patients.
- To determine if T cells targeting the stem cell marker OCT4 are operational in the immune response against ovarian cancer.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMCs) and ascites lymphocytes from healthy individuals and ovarian cancer patients.
- Identification and functional characterization of OCT4-specific CD4+ and CD8+ T cells using peptide and mRNA stimulation.
- Assessment of T cell proliferation, cytokine production (IFNγ, IP-10), and cytotoxic activity (CD107a mobilization).
Main Results:
- Naturally occurring OCT4-specific CD4+ and CD8+ T cells were identified in both healthy individuals and ovarian cancer patients.
- OCT4-reactive CD4+ T cells proliferated but did not produce IFNγ or IP-10.
- OCT4-reactive CD8+ T cells produced IFNγ and IP-10, and exhibited cytotoxic activity (CD107a mobilization).
Conclusions:
- The study demonstrates the existence of anti-CSC specific T cells in ovarian cancer patients.
- These findings suggest that OCT4-specific T cells, particularly CD8+ cytotoxic T cells, may play a role in controlling ovarian cancer and represent potential therapeutic targets.
