Recent Progress in the Synergistic Combination of Nanoparticle‐Mediated Hyperthermia and Immunotherapy for Treatment of Cancer

Abstract

Immunotherapy has demonstrated great clinical success in certain cancers, driven primarily by immune checkpoint blockade and adoptive cell therapies. Immunotherapy can elicit strong, durable responses in some patients, but others do not respond, and to date immunotherapy has demonstrated success in only a limited number of cancers. To address this limitation, combinatorial approaches with chemo‐ and radiotherapy have been applied in the clinic. Extensive preclinical evidence suggests that hyperthermia therapy (HT) has considerable potential to augment immunotherapy with minimal toxicity. This progress report will provide a brief overview of immunotherapy and HT approaches and highlight recent progress in the application of nanoparticle (NP)‐based HT in combination with immunotherapy. NPs allow for tumor‐specific targeting of deep tissue tumors while potentially providing more even heating. NP‐based HT increases tumor immunogenicity and tumor permeability, which improves immune cell infiltration and creates an environment more responsive to immunotherapy, particularly in solid tumors.

The Prediction Potential of the Pretreatment Lung Immune Prognostic Index for the Therapeutic Outcomes of Immune Checkpoint Inhibitors in Patients With Solid Cancer: A Systematic Review and Meta-Analysis

“…Immunotherapy has demonstrated great clinical success in certain cancers, but so far, immunotherapy has only achieved success in a limited number of cancers ( 32 ). Specifically, Callahan, M.K., et al.…”

Immunogenic Cell Death Induction by Ionizing Radiation

“…Hyperthermia (HT) is a cancer treatment strategy by raising tissue temperature to 39–45°C for a certain period of time and it has been reported in many phase II and phase III trials combined with radiotherapy and chemotherapy ( 88 , 89 ). HT can not only cause protein denaturation and aggregation to activate downstream pathways such as the DNA damage response to kill tumor cells directly but also induce ICD to reverse tumor immunosuppressive microenvironment and produce antitumor immunity ( 90 ).…”

Polymeric Nanosystems for Immunogenic Cell Death‐Based Cancer Immunotherapy

“…In particular, heating cervical tumors before vaginal hysterectomy significantly reduce the risk of tumor dissemination post-surgery, which exhibits the necessity of the time delay between tumor removal and tumor heating and inspires us to take the effect of local HT on antitumor immunotherapy into consideration. [34] As the studies on HT-related cancer immunotherapy grow, the fever-like temperature caused by HT has been proved to strengthen antigen presentation enhancement and trigger leukocyte recruitment in tumor site, which is not only beneficial for local tumors but also distant tumors due to systemic immune response. [2] The treatment of primary tumors and immune respond of the distant tumors need a balance to maximize the cancer therapy efficiency, preventing immune cell infiltration and immune induction from excessive high temperature.…”

“…[71] In this regard, the connection of SAR value and size distribution exhibits the negative correlation, which means the wider the size distribution of magnetic nanoparticles, the lower the SAR value and the more efficient magnetic-to-heat conversion. [34] In terms of chemical composition, transition metal cations (Co 2+ , Ni 2+ , Zn 2+ , or Mn 2+ ) upregulate SAR value and further active the magnetic capabilities of ferrite-based nanoparticles when they are doped at the specific locations like octahedral and tetrahedral sites. [72] As the aspect of morphology, in the case of the same size and composition, cubic nanoparticles generally show obviously higher SAR because of the increase of disordered spin on the surface of nanoparticles compare with the spherical nanoparticles.…”