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Generation of Lymph Node-fat Pad Chimeras for the Study of Lymph Node Stromal Cell Origin
Published on: December 16, 2013
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Induction of Tertiary Lymphoid Structures With Antitumor Function by a Lymph Node-Derived Stromal Cell Line
Genyuan Zhu1, Satoshi Nemoto1, Adam W Mailloux1
1Immunology Program, Moffitt Cancer Center, Tampa, FL, United States.
Frontiers in Immunology
|August 1, 2018
Summary
Tertiary lymphoid structures (TLSs) can be engineered using stromal lymph node (sLN) cells to enhance antitumor immunity. This approach suppresses tumor growth by boosting immune cell activity and downregulating immune checkpoints.
Area of Science:
- Immunology
- Cancer Biology
- Tissue Engineering
Background:
- Tertiary lymphoid structures (TLSs) are associated with improved cancer prognosis, but their formation and function are not fully understood.
- Stromal cells in lymph nodes (sLN) play key roles in lymphoid tissue organization and immune cell trafficking.
Purpose of the Study:
- To establish a mouse model for studying TLS formation and their contribution to antitumor immunity.
- To investigate the potential of sLN cells in inducing TLS formation.
Main Methods:
- A specific sLN cell line expressing lymphoid chemokines was selected.
- Subcutaneous injection of the sLN line was used to induce TLS formation in mice.
- The impact of TLSs on tumor growth and immune cell activity was assessed using MC38 tumor models.
Main Results:
- The sLN line successfully induced TLS formation, attracting host immune cells.
- TLS-residing lymphocytes, activated by tumor antigen-pulsed dendritic cells, exhibited specific cytotoxicity.
- The presence of TLSs suppressed MC38 tumor growth by enhancing antitumor immunity and downregulating PD-1 and Tim-3.
Conclusions:
- Stromal lymph node cells can be utilized to engineer functional tertiary lymphoid structures.
- Engineered TLSs demonstrate potential for enhancing antitumor immune responses and suppressing tumor growth.
- Further development of sLN cell lines could optimize TLS functions for cancer immunotherapy.
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