Immunomodulatory effects of ablation therapy on tumors: Potentials for combination with immunotherapy

Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients

“…Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways when combined with checkpoint modulator anti-PD-1 and toll-like receptor 9 agonist CpG in mice with breast cancer [ 32 ]. Our clinical studies showed that HIFU could significantly increase TILs, activated CTLs and NK cell populations along the ablation margins [ 13 ] as well as in the paracortex, leading to the relief of immune suppression of the primary tumor and TDLNs. These results provide the fundamental basis for the development of a novel therapeutic approach in which HIFU, as a local intervention, would be combined with systemic immunotherapy such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors to potentiate antitumor efficacy of checkpoint inhibition immunotherapy.…”

“…It is usually performed for patients with a solid tumor, intending to destroy all sites of the disease. In addition to local ablation, numerous studies have revealed that HIFU can trigger host immune responses [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. It is becoming increasingly evident that HIFU local therapy can have systemic antitumor immune effects, which may help the immune system reduce local recurrence and control metastases.…”

The Effects of Localized Heat on the Hallmarks of Cancer

“…[217] While these examples describe the immunostimulatory effects of hyperthermia, the ability of ablative temperatures to induce anti-tumor immune responses has been reviewed extensively elsewhere. [218,219] Higher temperatures have been suggested as more efficient at instigating anti-tumor immune responses as they are more prolific at inducing immunogenic cell death, [220] although in vivo studies have repeatedly confirmed that 42°C for 30 min is effective for inducing significant DAMP expression. [221][222][223] A number of reports have described adaptive responses with thermal ablation as a monotherapy via similar mechanisms to hyperthermia; [219,224] however, in the majority of cases, ablative therapies only achieve durable antitumor immune responses when applied in combination with immunotherapies.…”

“…[218,219] Higher temperatures have been suggested as more efficient at instigating anti-tumor immune responses as they are more prolific at inducing immunogenic cell death, [220] although in vivo studies have repeatedly confirmed that 42°C for 30 min is effective for inducing significant DAMP expression. [221][222][223] A number of reports have described adaptive responses with thermal ablation as a monotherapy via similar mechanisms to hyperthermia; [219,224] however, in the majority of cases, ablative therapies only achieve durable antitumor immune responses when applied in combination with immunotherapies. [218,225] Therefore, based on the literature described, adaptive immunity can indeed be induced by moderate hyperthermia and the HSP70 family appear to be one of the principal sources of this response.…”

“…Once further pre-clinical and clinical studies have confirmed the results previously reported, the scope for combining thermal treatments with immunotherapies to facilitate T cell (immune checkpoint inhibitors) and NK cell (cytokine activation therapy) responses can be fully appreciated. [219,239,240]…”