by ecancer reporter Janet Fricker

A US study published in Nature Immunology suggests that ionizing radiation (IR) used to eliminate tumours may paradoxically interfere with the immune system’s anti cancer response.

Although almost half of cancer patients are treated by radiotherapy, in most cases this treatment option fails to achieve a permanent cure.

One suggestion has been that irradiation induces inhibition of anticancer immune responses.

In the current study Miriam Merad and colleagues, from Icahn School of Medicine at Mount Sinai, New York, used a wide arsenal of ‘knockout’ and adoptive transfer technologies to demonstrate that irradiation mobilises embryo-derived Langerhan cells (LCs) located in the skin.

They showed that LCs exhibit a greater capacity to repair irradiation induced DNA damage than other cell types.

They found that the cyclin-dependent kinase inhibitor (CDKN1A) to be over expressed by LCs.

While LCs with ‘knock-out’ Cdlm1a-/- underwent apoptosis and accumulated DNA damage following IR treatment, wild type LCs up regulated major histocompatilibility complex class II molecules, migrated to the draining lymph nodes and induced an increase in tumour-infiltrating regulatory T cells (T reg cells) upon exposure to IR.

In contrast, Cdkn1a -/- did not induce increases in Treg.

It is thought such regulatory T cells could prevent the activation of anti-tumour immune responses and thereby promote resistance among any tumour cells surviving radiotherapy.

“Our findings suggest a means for manipulating the resistance of LCs to IR to enhance the response of cutaneous tumors to radiotherapy,” write the authors.

In an accompanying News &Views article, Laurence Zitvoel and Guido Kroemer, from Inserm, France, write, “The results … strongly suggest that whenever possible, irradiation of major skin areas should be avoided so that a minimum number of LCs (which are present solely in the epidermis) are mobilised for immunosuppression.”

Alternatively, they add, if skin exposure proves unavoidable, radiotherapy should be accompanied by treatments that keep Treg cells in check.

Reference

J Price, J Idoyaga, H Salmon, et al. CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation. Nature Immunology.  

L Zitvogel & G Kroemer. Subversion of anticancer immunesurveillance by radiotherapy. Nature Immunology.