In conclusion, our study shows that the therapeutic synergism between radiotherapy and HSP90 inhibition for the treatment of CRC is not only limited to the radiosensitizing effects of HSP90 inhibition but extends also to facilitated priming of anti-tumor immune mechanisms – specifically in case of Kras-driven tumors and at clinically relevant irradiation doses ≤ 5 Gy. Here, KRAS is linked to neoplasm.