Landscape of the Peripheral Immune Response Induced by Local Microwave Ablation in Patients with Breast Cancer

Abstract

Minimally invasive thermal therapies have been attempted in the treatment of breast cancer, and the immune response induced by these therapies has not been fully reported. A clinical trial is performed to determine the effect of microwave ablation (MWA) in the treatment of early‐stage breast cancer. The authors perform single‐cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from six patients before and after ablation. NK and CD8+T cells are activated by MWA of breast cancer, with the increased inhibitory signature of CD8+T cells but not dysfunctional. Enhanced co‐stimulatory signature of CD4+ T cells is observed and increased frequency of ICOS+CD4+ T cells after MWA is confirmed by flow cytometric analysis. After ablation, T‐cell clones expand with increased T‐cell receptor diversities. Activated antigen receptor‐mediated signaling pathways are found in B cells. Enhanced interactions between B cells and CD4+ T cells are found, indicating that B cells are important antigen‐presenting cells that initiate CD4+T cells in MWA‐induced immune response. Blockade of CTLA‐4 or PD‐1 of post‐MWA PBMCs show higher T‐cell activity than that of pre‐MWA PBMCs. This study provide global characteristics of MWA‐induced systemic immune response and pave a way for the identification of potential targets to improve the immune response.

Clinical application status and prospect of the combined anti-tumor strategy of ablation and immunotherapy

“…Therefore, the influencing factors for ablation combine therapy are more complex, including the optimal timing of immunotherapy, the choice of adjuvant immunotherapy, and application order of ablation and immunotherapy ( 101 ). Previous study indicated that ICIs treatment after MWA, PBMCs showed higher T-cell activity than that of pre-MWA treatment ( 102 ). Besides, Imiquimod treatment after cryoablation resulted in better tumor clearance (10/10 vs 3/7 tumors; p =0.0147) and overall treatment efficacy (9/10 vs 2/7 relapse-free tumors; p =0.0345) than immunotherapy before cryoablation in basal cell carcinoma according to Georgios Gaitanis et al ( 103 ).…”

Rational Nanomedicine Design Enhances Clinically Physical Treatment‐Inspired or Combined Immunotherapy

“…Macroscopically, MWA treatment was found to induce systemic immune responses and confirmed that B cells played an important role in MWA‐activated immune responses. [ 149 ]…”

“…Macroscopically, MWA treatment was found to induce systemic immune responses and confirmed that B cells played an important role in MWA-activated immune responses. [149] The relationship between the specific immune response and T-cell response and tumor treatment outcome was analyzed in the study conducted by Katharina et al who traced and assayed their levels in the peripheral blood of patients with liver cancer after MWA. [150] Several results were obtained, for example, 1) The TAAs for specifically activating T cell responses were enhanced after MWA.…”

Synergetic Thermal Therapy for Cancer: State-of-the-Art and the Future

“…Similarly, a couple of studies have been proposed to combine HIFU with immunotherapy. The advantages of such combination can be concluded as: (1) Thermal therapy induced increase of IFN- , HSP 27, HSP 70 concentrations and decrease of IL-10, IL-4, TGFb-1, and TGFb-2 concentrations to help improve the antigen-presenting capability [ 16 , 103 , 104 ]; (2) Combined treatments also resulted in increased concentrations of dendritic cells and decreased concentrations of IL-10 and CD4 Foxp3 , leading to more efficient priming and activation of T-cells [ 13 , 105 ]; (3) Combined therapy induced elevated long-term memory markers CD4 CD44 CD62 and CD8 CD44 CD62 for prevention of tumor recurrence and thus enhanced sensitization of ICIs therapy [ 106 ]. In addition, the mechanical effect of HIFU also plays a significant part in improving the anti-tumor immune response, as the addition of the microbubbles was found to have induced the Th1 reaction to strengthen the activity of DC and cytotoxic lymphocytes [ 107 ].…”

“…Thermal damages include but are not limited to (1) cell membrane collapse, protein denaturation, mitochondrial dysfunction, halted enzyme function for over 50 °C, (2) inhibition of DNA replication, halted metabolism, the release of chemokines & cytokines for 41–45 °C, (3) release of pro-inflammatory cytokines, tumor antigens, RNA, DNA, heat shock proteins (HSPs) & high mobility group protein B1 (HMGB1) and so on. Besides, more evidence from recent studies indicates that thermal therapy could induce the immune response [ 12 , 13 , 14 , 15 , 16 , 17 ]. In tumor-draining lymph nodes (TDLN), thermal therapy can double the expression of CCL21 to make up for the reduced T cell homing [ 18 ].…”