Tumor-draining lymph node is important for a robust abscopal effect stimulated by radiotherapy

Area of Science:

• Immunology
• Oncology
• Radiotherapy Research

Background:

• Radiotherapy (RT) can induce an antitumor immune response at both irradiated and distant tumor sites (abscopal effect).
• Tumor-draining lymph nodes (LNs) play a role in anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immune responses.
• The role of LNs in mediating RT-alone-induced abscopal responses remains unclear.

Purpose of the Study:

• To investigate if the tumor-draining lymph node (LN) mediates abscopal responses stimulated by radiotherapy alone.
• To explore the role of specific T-cell subsets within the LN during RT-induced abscopal effects.

Main Methods:

• Utilized a bilateral subcutaneous B16F10 flank tumor model in mice.
• Administered RT to one flank tumor or to both the tumor and its draining LN.
• Assessed tumor growth and analyzed T-cell populations (CD8+, stem-like CD8+) in tumors and LNs via flow cytometry.

Main Results:

• Local tumor irradiation demonstrated an abscopal effect, controlling distant tumor growth.
• Depletion of CD8+ T-cells significantly diminished the abscopal response.
• Tumor irradiation increased CD8+ and stem-like CD8+ T-cell proliferation within the LN.
• Targeting both the LN and tumor with RT reduced the abscopal effect and associated T-cell populations.

Conclusions:

• The tumor-draining lymph node (LN) is a key mediator of the abscopal effect.
• LNs serve as a reservoir and expansion site for stem-like CD8+ T-cells.
• These stem-like T-cells, originating from the LN, are crucial for populating tumors and mediating RT-induced abscopal responses.