Main Session
Sep 29
PQA 06 - Radiation and Cancer Biology, Health Care Access and Engagement

3171 - Antitumor Effect of PRaG Therapy in a Triple-Negative Breast Cancer Model

05:00pm - 06:00pm PT
Hall F
Screen: 13
POSTER

Presenter(s)

Jiaqi Zhang, - Center for Cancer Diagnosis and Treatment, The Second Af?liated Hospital of Soochow University, Suzhou, Jiangsu

J. Zhang1, K. Tan1, Y. Wu1, and L. Zhang2; 1Center of PRaG therapy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China, 2Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China

Purpose/Objective(s): Triple-negative breast cancer (TNBC) is highly aggressive, with a high recurrence rate and poor long-term outcomes from conventional chemotherapy. This study investigates a combination therapy using programmed cell death-1 (PD-1) inhibitors, radiotherapy, and granulocyte-macrophage colony-stimulating factor (GM-CSF), termed PRaG, as a potential treatment for murine TNBC, aiming to provide a foundation for clinical applications.

Materials/Methods:

  1. Antitumor Effect of PRaG Therapy in Murine TNBC Model: A bilateral subcutaneous tumor model of murine TNBC (4T1) was used. Tumor growth curves were compared among the following groups: control (CON), radiotherapy alone (8 Gy × 3 times) (Ra), radiotherapy combined with PD1 monoclonal antibody (PRa), and radiotherapy combined with PD1 monoclonal antibody and GM-CSF (PRaG).
  2. Effect of PRaG on Tumor Immune Microenvironment: Changes in immune cell proportions in the tumors were assessed in the PRaG group and corresponding controls.
  3. Role of T Lymphocytes and cDC1 Cells in Antitumor Effect: The contributions of CD4+ and CD8+ T lymphocytes and conventional type 1 dendritic cells (cDC1) to PRaG's antitumor effects were explored through T cell depletion and Batf3-/- (cDC1-deficient) mice.

Results:

  1. Tumor Growth Inhibition: In the murine TNBC model, the PRaG group showed significantly reduced tumor volume on both irradiated and non-irradiated sides compared to CON, Ra, and PRa groups (P < 0.05).
  2. Changes in Immune Cell Infiltration: PRaG therapy increased CD8+ T cell infiltration in non-irradiated tumors, though this was not statistically significant. PRaG also reduced the proportion of G-MDSC cells (P < 0.05) and increased cytokine secretion (TNFa, IFN?) by CD8+ T cells in the draining lymph nodes of irradiated tumors (P < 0.05).
  3. Impact of T Cell and cDC1 Depletion: Depletion of CD8+ T cells in PRaG-treated mice accelerated tumor growth on both sides (P < 0.001), while CD4+ T cell depletion had no significant effect. In Batf3-/- PRaG mice, tumor growth was significantly faster (P < 0.001 for irradiated side, P < 0.05 for non-irradiated side).

Conclusion: PRaG therapy inhibited tumor growth on both irradiated and non-irradiated sides. It achieved this by enhancing CD8+ T cell infiltration, reducing G-MDSC cells, and increasing cytokine secretion, thus inducing a distant antitumor effect. The immune-mediated antitumor effect of PRaG relies on CD8+ T cells, not CD4+ T cells, and the depletion of cDC1 cells abolishes this effect.