Opportunities and challenges in combining immunotherapy and radiotherapy in head and neck cancers

Wong, Kenneth C.W.; Johnson, David; Hui, Edwin P.; Lam, Rachel C. T.; B.Y., Brigette; Chan, Anthony T.C.

doi:10.1016/j.ctrv.2022.102361

Cited by 16 publications

(10 citation statements)

References 113 publications

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“…It is known that RT could kill tumor cells directly by causing DNA damage and oxidative stress via the overproduction of ROS. [ 42 ] Our findings showed that the ADU‐AAV‐PD1@Gel exhibited high ADU and AAV‐PD1‐loading efficiency and a ROS‐stimulus‐responsive release triggered by radiation both in vitro and in vivo. In addition, radiotherapy‐induced ICD of tumor cells can promote immune response, which has been recognized as a critical determinant of the efficacy of cancer therapy.…”

Section: Discussionmentioning

confidence: 87%

Immunostimulant In Situ Hydrogel Improves Synergetic Radioimmunotherapy of Malignant Glioblastoma Relapse Post‐Resection

Sun

et al. 2022

Adv Funct Materials

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Tumor recurrence remains the major cause of management failure after surgical resection of glioblastoma (GBM). Immunotherapy has the potential to effectively eradicate tumors and trigger immune memory to prevent tumor recurrence but not improve the outcomes of GBM patients. Here, an injectable, reactive oxygen species-degradable therapeutic hydrogel (ADU-AAV-PD1@Gel), capable of sustained local release of soluble PD-1 (sPD-1) and stimulator of interferon gene (STING) agonist ADU-S100 (ADU), is developed and applied in a GBM surgical resection model. Adeno-associated virus serotype 9 is employed to stably express sPD-1 blocking the PD-1/PD-L1 pathway. Concomitantly, the released ADU activates the STING pathway to improve tumor immunogenicity and response to therapy. This therapeutic hydrogel combined with radiotherapy (RT) effectively promotes sustained T cells infiltration and restores T cells effector function, which exhibits a robust antitumor immune response and significantly suppresses tumor growth. Moreover, ADU-AAV-PD1@Gel combined with RT treatment can also induce a long-term immune memory to prevent GBM recurrence. As a result, ADU-AAV-PD1@Gel provides a novel strategy for effective radioimmunotherapy of GBM relapse post-resection.

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Section: Discussionmentioning

confidence: 87%

Immunostimulant In Situ Hydrogel Improves Synergetic Radioimmunotherapy of Malignant Glioblastoma Relapse Post‐Resection

Sun

et al. 2022

Adv Funct Materials

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“…However, the prognosis of the aggressive subgroup is poor, with a median survival of only 11–22 months [ 10 ]. Molecular targeted therapy and immunotherapy have been employed to compensate for the deficiency of traditional treatments and showed satisfactory efficiency, which can supplement existing therapies [ 11 – 13 ]. Anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors (TKI), and VEGF inhibitors are the primary drugs for targeted molecular treatment of NPC, impacting many cancers combined with CT or concurrent chemoradiotherapy (CCRT) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic poly(A)-binding protein 1 (PABPC1) is a prognostic biomarker to predict survival in nasopharyngeal carcinoma regardless of chemoradiotherapy

Feng

et al. 2023

BMC Cancer

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Background Nasopharyngeal carcinoma (NPC), especially the nonkeratinizing type, is a malignant tumor primarily occurring in southern China and Southeast Asia. Chemotherapy (CT) and combined radiotherapy (RT) is used to treat NPC. However, the mortality rate is high in recurrent and metastatic NPC. We developed a molecular marker, analyzed its correlation with clinical characteristics, and assessed the prognostic value among NPC patients with or without chemoradiotherapy. Methods A total of 157 NPC patients were included in this study, with 120 undergoing treatment and 37 without treatment. EBER1/2 expression was investigated using in situ hybridization (ISH). Expression of PABPC1, Ki-67, and p53 was detected with immunohistochemistry. The correlations of EBER1/2 and the expression of the three proteins having clinical features and prognosis were evaluated. Results The expression of PABPC1 was associated with age, recurrence, and treatment but not with gender, TNM classification, or the expression of Ki-67, p53, or EBER. High expression of PABPC1 was associated with poor overall survival (OS) and disease-free survival (DFS) and was an independent predictor depending on multivariate analysis. Comparatively, no significant correlation was observed between the expression of p53, Ki-67, and EBER and survival. In this study, 120 patients received treatments and revealed significantly better OS and DFS than the untreated 37 patients. PABPC1 high expression was an independent predictor of shorter OS in the treated (HR = 4.012 (1.238–13.522), 95% CI, p = 0.021) and the untreated groups (HR = 5.473 (1.051–28.508), 95% CI, p = 0.044). However, it was not an independent predictor of shorter DFS in either the treated or the untreated groups. No significant survival difference was observed between patients with docetaxel-based induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and those with paclitaxel-based IC + CCRT. However, when combined with treatment and PABPC1 expression, patients with paclitaxel-added chemoradiotherapy plus PABPC1 low expression had significantly better OS than those who underwent chemoradiotherapy (p = 0.036). Conclusions High expression of PABPC1 is associated with poorer OS and DFS among NPC patients. Patients with PABPC1 having low expression revealed good survival irrespective of the treatment received, indicating that PABPC1 could be a potential biomarker for triaging NPC patients.

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“…In the case of HNSCC, radiation therapy is a standard treatment method that shows a better response in human papillomavirus (HPV) - positive patients than in HPV-negative ones ( 69 ). The virus-induced cancers display different biological and clinical characteristics but also dissimilar immune landscapes compared to their negative counterparts ( 70 ). A multicentre study analyzed the prognostic value of CD8+ and CD3+ T cells in correlation with HPV status in patients with HNSCC that underwent CRT treatment ( 71 ).…”

Section: Immune Landscape and Radiotherapymentioning

confidence: 99%

The current understanding of the immune landscape relative to radiotherapy across tumor types

et al. 2023

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Radiotherapy is part of the standard of care treatment for a great majority of cancer patients. As a result of radiation, both tumor cells and the environment around them are affected directly by radiation, which mainly primes but also might limit the immune response. Multiple immune factors play a role in cancer progression and response to radiotherapy, including the immune tumor microenvironment and systemic immunity referred to as the immune landscape. A heterogeneous tumor microenvironment and the varying patient characteristics complicate the dynamic relationship between radiotherapy and this immune landscape. In this review, we will present the current overview of the immunological landscape in relation to radiotherapy in order to provide insight and encourage research to further improve cancer treatment. An investigation into the impact of radiation therapy on the immune landscape showed in several cancers a common pattern of immunological responses after radiation. Radiation leads to an upsurge in infiltrating T lymphocytes and the expression of programmed death ligand 1 (PD-L1) which can hint at a benefit for the patient when combined with immunotherapy. In spite of this, lymphopenia in the tumor microenvironment of ‘cold’ tumors or caused by radiation is considered to be an important obstacle to the patient’s survival. In several cancers, a rise in the immunosuppressive populations is seen after radiation, mainly pro-tumoral M2 macrophages and myeloid-derived suppressor cells (MDSCs). As a final point, we will highlight how the radiation parameters themselves can influence the immune system and, therefore, be exploited to the advantage of the patient.

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Opportunities and challenges in combining immunotherapy and radiotherapy in head and neck cancers

Cited by 16 publications

References 113 publications

Immunostimulant In Situ Hydrogel Improves Synergetic Radioimmunotherapy of Malignant Glioblastoma Relapse Post‐Resection

Immunostimulant In Situ Hydrogel Improves Synergetic Radioimmunotherapy of Malignant Glioblastoma Relapse Post‐Resection

Cytoplasmic poly(A)-binding protein 1 (PABPC1) is a prognostic biomarker to predict survival in nasopharyngeal carcinoma regardless of chemoradiotherapy

The current understanding of the immune landscape relative to radiotherapy across tumor types

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