Carbon ion radiotherapy (CIRT) alone leads to a reduction of lung metastases in an osteosarcoma in vivo model, which is not the case for conventional photon therapy (XRT), when compared to untreated negative controls (NC). Addition of immunotherapy (Figure 1: a mix checkpoint inhibitors, CPI) fosters the immunogenic response, leading to further reduction of lung metastases. This shows the vast potential for CIRT as a match in combination with immunotherapy in terms of checkpoint blockade [17].

Dr. Silvana Miranda

Head and neck squamous cell carcinomas (HNSCC) comprise a group of malignancies classified according to their anatomical site of origin (Figure 3). They are among the most common cancers worldwide and represent a major global health burden [20]. Radiotherapy is one key player in the treatment of HNSCC, however, it may cause challenging side effects that have a big impact on the patient’s quality of life [20, 21]. Additionally, HNSCC display marked heterogeneity in their tumor biology, depending on whether or not there is an human papilloma virus (HPV) infection [22]. HPV-positive tumors typically more sensitive to radiation and are generally more recognized by the immune system and respond better to treatment [23, 24]. On the other hand HPV-negative tumors are known to be more resistant to therapy, have poorer clinical outcomes and create an immunosuppressive microenvironment [22, 25]. Carbon ion radiotherapy (CIRT), due to its inverted dose-depth profile, offers superior dose conformity and sparing of surrounding tissues, which is particularly valuable in the anatomically complex head and neck region, helping prevent radiation-induced side effects [26, 27]. Additionally, in vitro  studies have shown a decreased survival of HPV-negative cell lines compared to photon irradiation (Figure 4) [28]. Moreover, CIRT causes complex DNA damage on the cancer cells, activates distinct cell death pathways, and potentially, induces a more robust immune system activation, compared to conventional radiotherapy modalities [27, 29].

In our research, we investigate how CIRT can modulate radiation responses, tumor control and immune activation mechanisms in oral carcinoma model, with different HPV backgrounds. We address these questions using a combined in vitro and in vivo approach, including oral cancer cell lines engineered to express HPV derived oncoproteins, that are used to investigate radiation immune system activation responses.