Oral Candida in post-radiotherapy patients with xerostomia/hyposalivation: A narrative review.

OBJECTIVE: Head and Neck Cancer (HNC) patients receiving radiotherapy (RT) often suffer from xerostomia and/or hyposalivation. As saliva plays an important antimicrobial and cleansing roles, these patients are at higher risks of opportunistic infections. This narrative review aims to provide an overview of current evidence on oral Candida colonisation and infection in these patients. METHODS: A literature review of clinical studies on oral Candida colonisation and candidiasis in HNC patients receiving radiotherapy/chemoradiotherapy was conducted. RESULTS: Many clinical studies found high levels of Candida colonisation and a substantial proportion of post-RT HNC patients suffering from oropharyngeal candidiasis (OPC). Importantly, oral Candida could be a reservoir for life-threatening systemic infection in immunocompromised patients. The rising prevalence of non-albicans Candida species and drug-resistant infections has made identification of Candida species and antifungal susceptibility more important. Recent advances in oral microbiome and its interactions with Candida are discussed. This review also offers perspectives on limitations of current evidence and suggestions for future research. CONCLUSION: Further research to better understand Candida carriage, microbiome, OPC, and xerostomia/hyposalivation post-RT would aid in devising a more comprehensive long-term management plan and novel therapeutic approaches for HNC patients to achieve the full benefits of RT while minimising side effects.

Assessment of the Dietary Intake Changes in Patients with Head and Neck Cancer Treated with Radical Radiotherapy.

BACKGROUND: Patients during radiotherapy due to head and neck cancers experience a lot of side effects which may have a considerable impact on the patients' ability to meet individual daily energy demands by means of oral diet. METHODS: The study included 104 head and neck cancer patients who qualified for radical radiotherapy. Radical treatment takes 6 weeks and every week the patients were assessed for dietary intake. The subjects were covered with the constant care of a dietician, received FSMP (food for special medical purposes), and, if necessary, enteral nutrition. RESULTS: In the first week of treatment, the patients, from the kitchen diet alone, met 91.5% of the energy demand, while in the last week of treatment, only 40.9%. After introducing the FSMP or enteral nutrition, the patients met 120% of the demand in the first week of therapy and 95% in the last week, respectively. The patients who followed the dietary recommendations were characterized by significantly lower weight loss (3.07 kg) compared to non-adherent patients (5.56 kg). CONCLUSIONS: The used therapy significantly contributed to decreasing nutritional intake in the subsequent weeks of treatment. On the other hand, incorporating FSMP in the diet and enteral nutrition with industrial diets significantly increased the fulfilled energy demand of patients.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells.

Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rß, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis in vitro. N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with cyclin D downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and FasL in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.

Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors.

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence. Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors. Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors. Discussion: Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.

Advances in human papillomavirus detection and molecular understanding in head and neck cancers: Implications for clinical management.

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.

TransAnaNet: Transformer-based Anatomy Change Prediction Network for Head and Neck Cancer Patient Radiotherapy.

Background: Adaptive radiotherapy (ART) can compensate for the dosimetric impact of anatomic change during radiotherapy of head neck cancer (HNC) patients. However, implementing ART universally poses challenges in clinical workflow and resource allocation, given the variability in patient response and the constraints of available resources. Therefore, early identification of head and neck cancer (HNC) patients who would experience significant anatomical change during radiotherapy (RT) is of importance to optimize patient clinical benefit and treatment resources. Purpose: The purpose of this study is to assess the feasibility of using a vision-transformer (ViT) based neural network to predict radiotherapy induced anatomic change of HNC patients. Methods: We retrospectively included 121 HNC patients treated with definitive RT/CRT. We collected the planning CT (pCT), planned dose, CBCTs acquired at the initial treatment (CBCT01) and fraction 21 (CBCT21), and primary tumor volume (GTVp) and involved nodal volume (GTVn) delineated on both pCT and CBCTs for model construction and evaluation. A UNet-style ViT network was designed to learn the spatial correspondence and contextual information from embedded image patches of CT, dose, CBCT01, GTVp, and GTVn. The deformation vector field between CBCT01 and CBCT21 was estimated by the model as the prediction of anatomic change, and deformed CBCT01 was used as the prediction of CBCT21. We also generated binary masks of GTVp, GTVn and patient body for volumetric change evaluation. We used data from 100 patients for training and validation, and the remaining 21 patients for testing. Image and volumetric similarity metrics including mean square error (MSE), structural similarity index (SSIM), dice coefficient, and average surface distance were used to measure the similarity between the target image and predicted CBCT. Results: The predicted image from the proposed method yielded the best similarity to the real image (CBCT21) over pCT, CBCT01, and predicted CBCTs from other comparison models. The average MSE and SSIM between the normalized predicted CBCT to CBCT21 are 0.009 and 0.933, while the average dice coefficient between body mask, GTVp mask, and GTVn mask are 0.972, 0.792, and 0.821 respectively. Conclusions: The proposed method showed promising performance for predicting radiotherapy induced anatomic change, which has the potential to assist in the decision making of HNC Adaptive RT.

Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Advancing Head and Neck Cancer Survival Prediction via Multi-Label Learning and Deep Model Interpretation.

A comprehensive and reliable survival prediction model is of great importance to assist in the personalized management of Head and Neck Cancer (HNC) patient treated with curative Radiation Therapy (RT). In this work, we propose IMLSP, an Interpretable Multi-Label multi-modal deep Survival Prediction framework for predicting multiple HNC survival outcomes simultaneously and provide time-event specific visual explanation of the deep prediction process. We adopt Multi-Task Logistic Regression (MTLR) layers to convert survival prediction from a regression problem to a multi-time point classification task, and to enable predicting of multiple relevant survival outcomes at the same time. We also present Grad-Team, a Gradient-weighted Time-event activation mapping approach specifically developed for deep survival model visual explanation, to generate patient-specific time-to-event activation maps. We evaluate our method with the publicly available RADCURE HNC dataset, where it outperforms the corresponding single-modal models and single-label models on all survival outcomes. The generated activation maps show that the model focuses primarily on the tumor and nodal volumes when making the decision and the volume of interest varies for high- and low-risk patients. We demonstrate that the multi-label learning strategy can improve the learning efficiency and prognostic performance, while the interpretable survival prediction model is promising to help understand the decision-making process of AI and facilitate personalized treatment. The project website can be found at https://github.com/***.

Transcription Factors and Markers Related to Epithelial-Mesenchymal Transition and Their Role in Resistance to Therapies in Head and Neck Cancers.

Head and neck cancers (HNCs) are heterogeneous and aggressive tumors of the upper aerodigestive tract. Although various histological types exist, the most common is squamous cell carcinoma (HNSCC). The incidence of HNSCC is increasing, making it an important public health concern. Tumor resistance to contemporary treatments, namely, chemo- and radiotherapy, and the recurrence of the primary tumor after its surgical removal cause huge problems for patients. Despite recent improvements in these treatments, the 5-year survival rate is still relatively low. HNSCCs may develop local lymph node metastases and, in the most advanced cases, also distant metastases. A key process associated with tumor progression and metastasis is epithelial-mesenchymal transition (EMT), when poorly motile epithelial tumor cells acquire motile mesenchymal characteristics. These transition cells can invade different adjacent tissues and finally form metastases. EMT is governed by various transcription factors, including the best-characterized TWIST1 and TWIST2, SNAIL, SLUG, ZEB1, and ZEB2. Here, we highlight the current knowledge of the process of EMT in HNSCC and present the main protein markers associated with it. This review focuses on the transcription factors related to EMT and emphasizes their role in the resistance of HNSCC to current chemo- and radiotherapies. Understanding the role of EMT and the precise molecular mechanisms involved in this process may help with the development of novel anti-cancer therapies for this type of tumor.

The Use of Artificial Intelligence in Head and Neck Cancers: A Multidisciplinary Survey.

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits.

Comparison of Submental Surface Electromyography during Dry Swallow between Irradiated Head and Neck Cancer Survivors and Normal Individuals.

INTRODUCTION: This study compared the submental surface electromyography (sEMG) duration and amplitude during dry swallowing between irradiated head and neck cancer (HNC) survivors and age-matched normal individuals. Further, the relationship between submental and infrahyoid sEMG in the irradiated HNC group was explored. METHOD: Forty participants (20 HNC survivors and 20 age-matched normal individuals) participated in this study. The HNC survivors had completed organ preservation cancer treatment (at least 1-month post-treatment). They were on a complete oral diet without enteral supplementation (FOIS score> 4). Submental and infrahyoid sEMG activity was calculated for three trials of saliva swallow for each participant using sEMG. The duration and amplitude parameters considered were: onset duration - duration from the onset of swallowing to the maximum amplitude, offset duration - duration from the maximum amplitude to the end of the swallowing activity, total duration, and maximum amplitude. RESULTS: The study found that irradiated HNC survivors exhibited prolonged temporal measures, particularly in the offset duration, which suggested a delayed descent of the hyolaryngeal complex during swallowing. Additionally, the HNC group showed a positive correlation between submental and infrahyoid sEMG. Furthermore, it was observed that the rate of increase in the duration of submental sEMG during subsequent swallowing was greater in HNC survivors which could be due to reduced salivation. CONCLUSION: Compared to age-matched normal individuals, irradiated HNC survivors manifest alterations in the submental muscle activities during dry swallowing as measured using sEMG. The temporal and amplitude changes are likely to have arisen as a consequence of postradiation changes.

Rapamycin alleviates irradiation-induced parotid injury by enhancing the whole gland homeostasis.

OBJECTIVES: Salivary gland injury is one of the most common complications of radiotherapy in head-and-neck cancers. This study investigated the mechanism by which rapamycin prevents irradiation (IR)-induced injury in the parotid glands. MATERIALS AND METHODS: Miniature pigs either received (a) no treatment (NT), (b) IR in the right parotid gland for 5 consecutive days (IR), or intraperitoneal administration of rapamycin (Rap) 1 h prior to IR (IR + Rap). Tissues were collected at three distinct time points (24 h, 4 weeks, and 16 weeks) after IR. Histological analyses, western blot, and real-time reverse transcriptase-polymerase chain reaction were performed to explore the mechanisms of IR-induced injury in the parotid gland. RESULTS: Rapamycin treatment maintained parotid salivary flow 16 weeks post-IR, preserved the number of acinar cells, and reduced parotid tissue fibrosis, as well as reduced apoptosis levels, decreased cleaved caspase-3 expression, and increased the Bcl-2/Bax ratio in the parotid glands. Autophagy marker LC3B was upregulated by rapamycin after IR, while P62 expression was downregulated. Rapamycin reduced the expression of pro-inflammatory factors and the mesenchymal tissue fibrosis following IR. CONCLUSIONS: Rapamycin maintains gland homeostasis after IR by decreasing apoptosis, reducing the expression of pro-inflammatory factors, and enhancing autophagy.

Can Lateral Thoracic Artery Preservation Improve Results in Large PMMC Flaps? - Our Experience of 61 Cases from Northern India.

Introduction: Pectoralis major myo-cutaneous (PMMC) flap continues to be a widely used tool to reconstruct oral cavity defects. But an unreliable and unstable vascular supply can lead to complications like flap loss, Oro-cutaneous fistula and wound dehiscence. Preservation of the lateral thoracic artery (LTA) has been suggested to improve the vascularity of the skin paddle. The present study aspires to compare the complications and flap related outcomes after preserving or sacrificing the LTA while reconstructing oral cavity defects with bi-folded PMMC flap. Materials and Methods: Retrospective analysis of the data of 61 male patients who were reconstructed with bi-folded PMMC flaps between January 2022 and September 2022 was done. 36 patients were reconstructed using a PMMC flap where the LTA was sacrificed, whereas in 25 patients the LTA was preserved. Data was analyzed in terms of patient factors and flap related complications. Results: The overall complication rate including major/minor complications was 44.26% with flap detachment at 22.95% being the commonest complication observed. 13.11% patients developed an Oro-cutaneous fistula and partial and complete flap loss were seen in 9.83% and 4.91% respectively. LTA preservation was significantly associated with only decreased flap detachment rates (p value < 0.05). No significant association was noticed between other flap related complications and LTA preservation. Conclusion: Reconstructing larger defects with a PMMC flap where the LTA is preserved can help improve the vascularity of the flap and decrease various major/minor flap related complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04123-3.

Twelve years after: The french national network on rare head and neck tumours (REFCOR).

BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

Anti-cancer management of head and neck cancers and oral microbiome-what can we clinically obtain?

Head and neck squamous cell carcinoma (HNSCC) exhibits significant genetic heterogeneity and primarily concerns the oral cavity and oropharynx. These cancers occur more frequently in men with a 5-year survival rate below 50%. Major risk factors include human papilloma virus (HPV) (notably type 16), Epstein-Barr virus, tobacco, alcohol, and poor oral hygiene with approximately 4.5% of global cancers linked to HPV. Notably, differences in the microbiome between healthy individuals and patients with head and neck cancers (HNCs) have been identified. Recent studies highlight the significance of certain oral microbes in risk assessment and the potential of the microbiome as a biomarker for HNCs. Additionally, role of the microbiome in metastasis has been acknowledged. Treatment for HNCs includes local methods, such as surgery and radiotherapy, and systemic approaches, such as immunotherapy. Numerous side effects accompany these treatments. Emerging research suggests the beneficial role of preoperative immunonutrition and probiotics in patient outcomes, emphasizing the influence of the microbiome on treatment efficacy. This review explores the reciprocal effects of HNC treatment and the gut microbiome using radiotherapy, brachytherapy, surgery, immunotherapy, and chemotherapy.

From Pixels to Diagnosis: Algorithmic Analysis of Clinical Oral Photos for Early Detection of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies. Despite numerous advancements in understanding its biology, the mean five-year survival rate of OSCC is still very poor at about 50%, with even lower rates when the disease is detected at later stages. We investigate the use of clinical photographic images taken by common smartphones for the automated detection of OSCC cases and for the identification of suspicious cases mimicking cancer that require an urgent biopsy. We perform a retrospective study on a cohort of 1470 patients drawn from both hospital records and online academic sources. We examine various deep learning methods for the early detection of OSCC cases as well as for the detection of suspicious cases. Our results demonstrate the efficacy of these methods in both tasks, providing a comprehensive understanding of the patient's condition. When evaluated on holdout data, the model to predict OSCC achieved an AUC of 0.96 (CI: 0.91, 0.98), with a sensitivity of 0.91 and specificity of 0.81. When the data are stratified based on lesion location, we find that our models can provide enhanced accuracy (AUC 1.00) in differentiating specific groups of patients that have lesions in the lingual mucosa, floor of mouth, or posterior tongue. These results underscore the potential of leveraging clinical photos for the timely and accurate identification of OSCC.

Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.

Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.