Radiotherapy is a cancer treatment that uses irradiation to damage tumor cells and induce their death. As cancer cells die and release their antigens, the irradiation also acts like an anti-tumor vaccine, since immune cells within and around the tumor recognize these antigens and initiate anti-tumor responses. This makes the combination of radiotherapy and immunotherapy with immune checkpoint inhibitors (ICIs) particularly interesting and potentially effective. ICIs enhance the immune system’s anti-tumor activity, enabling the body to destroy the cancer itself. However, in addition to damaging cancer cells, irradiation also harms immune cells within the tumor, which reduces the therapeutic effect. Therefore, a novel approach called partial irradiation (pIR) is being investigated, in which only part of the tumor is irradiated. This aims to stimulate the immune system without destroying all the immune cells.

In a recent study by Pišljar et al., the team investigated whether pIR combined with ICI immunotherapy could increase treatment efficacy. They compared pIR with full tumor irradiation (IR) in immune-cold mouse models of oral squamous cell carcinoma, a cancer typically treated with radiotherapy. Eighteen immune cell subpopulations in tumors were thoroughly evaluated before and after therapy using flow cytometry.

Key findings of the study:

  • Both pIR and IR caused a temporary influx of immune cells into tumors.
  • IR was more effective at suppressing tumor growth ; however, pIR combined with ICI immunotherapy significantly improved survival in one of the tumor models.
  • The combination treatment increased the number of lymphocytes in tumors.
  • Responses varied: responders had more cytotoxic T lymphocytes, whereas non-responders showed an accumulation of neutrophils, which are immunosuppressive cells that inhibit immune function.

The study demonstrates that pIR can stimulate the immune system comparably to IR, especially when combined with ICI immunotherapy. This represents an important step in developing new combination treatment strategies. Using pIR could reduce the side effects of IR, which is particularly significant for head and neck tumors due to the proximity of critical anatomical structures.

The full article is available at the following link:

https://www.sciencedirect.com/science/article/pii/S0753332225003014?via%3Dihub

Graphical abstract of the article