*Review* **Superparamagnetic Iron Oxide Nanoparticles for Immunotherapy of Cancers through Macrophages and Magnetic Hyperthermia**

**Alexandre M. M. Dias 1,†, Alan Courteau 1,2,†, Pierre-Simon Bellaye 1,3, Evelyne Kohli 3,4, Alexandra Oudot <sup>1</sup> , Pierre-Emmanuel Doulain <sup>5</sup> , Camille Petitot <sup>1</sup> , Paul-Michael Walker 1,2,4, Richard Decréau <sup>6</sup> and Bertrand Collin 1,6,\***


**Abstract:** Cancer immunotherapy has tremendous promise, but it has yet to be clinically applied in a wider variety of tumor situations. Many therapeutic combinations are envisaged to improve their effectiveness. In this way, strategies capable of inducing immunogenic cell death (e.g., doxorubicin, radiotherapy, hyperthermia) and the reprogramming of the immunosuppressive tumor microenvironment (TME) (e.g., M2-to-M1-like macrophages repolarization of tumor-associated macrophages (TAMs)) are particularly appealing to enhance the efficacy of approved immunotherapies (e.g., immune checkpoint inhibitors, ICIs). Due to their modular construction and versatility, iron oxide-based nanomedicines such as superparamagnetic iron oxide nanoparticles (SPIONs) can combine these different approaches in a single agent. SPIONs have already shown their safety and biocompatibility and possess both drug-delivery (e.g., chemotherapy, ICIs) and magnetic capabilities (e.g., magnetic hyperthermia (MHT), magnetic resonance imaging). In this review, we will discuss the multiple applications of SPIONs in cancer immunotherapy, focusing on their theranostic properties to target TAMs and to generate MHT. The first section of this review will briefly describe immune targets for NPs. The following sections will deal with the overall properties of SPIONs (including MHT). The last section is dedicated to the SPION-induced immune response through its effects on TAMs and MHT.

**Keywords:** cancer; immunotherapy; superparamagnetic iron oxide; nanoparticles; macrophages; magnetic hyperthermia; theranostics
