Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that develops in or around the throat, larynx, nose, sinuses and mouth, and is mostly treated with a combination of chemo- and radiotherapy (RT). The main goal of RT is to kill enough of the cancer cell population, whilst preserving the surrounding normal and healthy tissue. The mechanisms by which conventional photon RT achieves this have been extensively studied over several decades, but little is known about the cell death pathways that are activated in response to RT of increasing linear energy transfer (LET), including proton beam therapy and heavy ions. Here, we provide an up-to-date review on the observed radiobiological effects of low- versus high-LET RT in HNSCC cell models, particularly in the context of specific cell death mechanisms, including apoptosis, necrosis, autophagy, senescence and mitotic death. We also detail some of the current therapeutic strategies targeting cell death pathways that have been investigated to enhance the radiosensitivity of HNSCC cells in response to RT, including those that may present with clinical opportunities for eventual patient benefit.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with reported incidences of ~800 000 cases each year. One of the critical determinants in patient response to radiotherapy, particularly for oropharyngeal cancers, is human papillomavirus (HPV) status where HPV-positive patients display improved survival rates and outcomes particularly because of increased responsiveness to radiotherapy. The increased radiosensitivity of HPV-positive HNSCC has been largely linked with defects in the signalling and repair of DNA double-strand breaks. Therefore, strategies to further radiosensitise HPV-positive HNSCC, but also radioresistant HPV-negative HNSCC, have focussed on targeting key DNA repair proteins including PARP, DNA-Pk, ATM and ATR. However, inhibitors against CHK1 and WEE1 involved in cell-cycle checkpoint activation have also been investigated as targets for radiosensitisation in HNSCC. These studies, largely conducted using established HNSCC cell lines in vitro, have demonstrated variability in the response dependent on the specific inhibitors and cell models utilised. However, promising results are evident targeting specifically PARP, DNA-Pk, ATR and CHK1 in synergising with radiation in HNSCC cell killing. Nevertheless, these preclinical studies require further expansion and investigation for translational opportunities for the effective treatment of HNSCC in combination with radiotherapy.

Le traitement par radiothérapie des cancers des sphères thoracique, médiastinale et ORLest associé à un risque de complications cardiovasculaires. Les patients traités et guérisde leur cancer sont de plus en plus nombreux, vivent de plus en plus longtemps, et leurdevenir à long terme doit être pris en considération. Les complications cardiovasculairesassociées principalement au traitement des cancers du sein, du lymphome de Hodgkin et destumeurs de la tête et du cou se manifestent de manière insidieuse et chronique. Leursurvenue est liée à de nombreux facteurs comme l’âge du patient au moment du traitement,le nombre d’années suivant la radiothérapie, la dose et le volume au cœur et aux grosvaisseaux (artères coronaires et carotides) ou encore l’association avec les autresfacteurs de risque cardiovasculaire traditionnels. Les mécanismes physiopathologiques sontmal connus. Même si des similitudes avec l’athérosclérose liée à l’âge sont établies, lesspécificités et les particularités de l’athérosclérose radio-induite pour des fortes dosesd’irradiation restent à établir. Pour des faibles niveaux d’exposition aux rayonnementsionisants, des études épidémiologiques récentes suggèrent aussi un risque accru dedévelopper des pathologies cardiovasculaires. L’amélioration des connaissances sur lesmécanismes lésionnels à l’origine des pathologies cardiovasculaires radio-induites etl’identification plus précise des populations à risque devraient permettre dans le futurune prise en charge plus efficace de ces patients à risque vasculaire.

The general objective of the OSPAR radioactive substances strategy is to preventpollution of the maritime area from ionising radiation through progressive and substantialreductions of discharges, emissions and losses of radioactive substances, so thatconcentrations in the environment are close to background for naturally occurringradioactive substances and close to zero for artificial radioactive substances. The thirdperiodic evaluation of progress towards the objective of the OSPAR radioactive substancesstrategy concludes that, due to issues concerning the availability of reported data, it isnot possible to come to firm conclusions as to whether the aims of the OSPAR radioactivesubstances strategy are currently being delivered. However, in general there is anindication of a reduction in average marine concentrations of selected radionuclidesassociated with the nuclear industry, while doses arising from these selectedradionuclides in the OSPAR maritime area to humans are well within internationallyrecommended limits and are below the lowest levels at which any effects are likely tooccur for marine biota.

Le Laboratoire de Physique Électronique des Solides (LPES) de l'université de Nice-Sophia Antipolis (UNSA) est membre fondateur des « Laboratoires Associés en Dosimétrie et en Radiophysique » (LARD). Depuis, les travaux effectués au LPES s'inscrivent dans le cadre des LARD. Nous essayons, ici, de retracer vingt ans de recherches effectuées en relation avec la dosimétrie des rayonnements ionisants et l'interaction rayonnement-matière.