Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

Özcan-Wahlbrink, Mine; Schifflers, Christoph; Riemer, Angelika B.

doi:10.3389/fimmu.2019.02831

Cited by 17 publications

(14 citation statements)

References 84 publications

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“…Additional work on oropharyngeal SCC has confirmed a higher degree of infiltration of CD8+ T-cells in HPV-positive vs HPV-negative tumors ( 35 ). Overall, these studies suggest that the increased sensitivity of HPV-associated oropharyngeal SCC to chemotherapy and radiation therapy may at least in part be mediated through immune mechanisms ( 36 , 37 ), and that differing immunotherapeutic approaches may be optimal for HPV-positive and HPV-negative HNSCC.…”

Section: Immune Landscape Of Hnsccmentioning

confidence: 96%

Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges

Qian

Schoenfeld

2021

Front. Oncol.

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Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment over the past decade. However, although the immune landscape suggests a strong rationale for the use of these agents in patients with head and neck squamous cell carcinoma, the available clinical evidence indicates that most patients currently do not respond to ICI monotherapy. Radiotherapy is a primary treatment modality for many patients with locally advanced head and neck cancer. While ionizing radiation traditionally has been thought to act in a purely cytotoxic fashion, a growing body of preclinical studies have demonstrated additional profound immunomodulatory effects. Consequently, there has been a surge of interest in the potential synergy between radiotherapy and immunotherapy, both the potential for radiotherapy to augment the systemic anti-tumor immune response and the potential for immunotherapy to improve in-field tumor response to radiation. In this review, we summarize the current preclinical and clinical evidence for radioimmunotherapy, with a particular focus on studies directly relevant to head and neck squamous cell carcinoma, as well as existing challenges and future directions for this emerging field.

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Section: Immune Landscape Of Hnsccmentioning

confidence: 96%

Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges

Qian

Schoenfeld

2021

Front. Oncol.

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“…On the other hand, HPV + cancers show amplification and overexpression of p16 and E2F1 (1, 82). These differences have been attributed to the distinct responsiveness of the two subtypes to standard treatments, and may also be potentially exploited for targeted therapy (3,84). A case in point is the study by Gottgens EL et al which targeted CDK4/6 and showed that Palbocyclib is effective in increasing the radio-sensitivity of HPVcells (85).…”

Section: Targeting Cell Cycle Regulationmentioning

confidence: 99%

“…Also, HPV + -HNSCC primarily originates in the more lymphoid-dense regions of the head and neck. These differences certainly influence the unique recruitment of immune cells and the resulting landscape seen in the two cancers ( 84 ). Indeed, research data show that HPV + -HNSCC is richer and more diverse immunologically in terms of both gene expression and cellular composition.…”

Section: Targeting the Tumor Microenvironment Of Hpv +- Hnsccmentioning

confidence: 99%

Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review

Chitsike

Duerksen-Hughes

2021

Front. Oncol.

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The treatment landscape of locally advanced HPV-oropharyngeal squamous cell carcinoma (OPSCC) is undergoing transformation. This is because the high cures rates observed in OPSCC are paired with severe treatment-related, long-term toxicities. These significant adverse effects have led some to conclude that the current standard of care is over-treating patients, and that de-intensifying the regimens may achieve comparable survival outcomes with lower toxicities. Consequently, several de-escalation approaches involving locally advanced OPSCC are underway. These include the reduction of dosage and volume of intensive cytotoxic regimens, as well as elimination of invasive surgical procedures. Such de-intensifying treatments have the potential to achieve efficacy and concurrently alleviate morbidity. Targeted therapies, given their overall safer toxicity profiles, also make excellent candidates for de-escalation, either alone or alongside standard treatments. However, their role in these endeavors is currently limited, because few targeted therapies are currently in clinical use for head and neck cancers. Unfortunately, cetuximab, the only FDA-approved targeted therapy, has shown inferior outcomes when paired with radiation as compared to cisplatin, the standard radio-sensitizer, in recent de-escalation trials. These findings indicate the need for a better understanding of OPSCC biology in the design of rational therapeutic strategies and the development of novel, OPSCC-targeted therapies that are safe and can improve the therapeutic index of standard therapies. In this review, we summarize ongoing research on mechanism-based inhibitors in OPSCC, beginning with the salient molecular features that modulate tumorigenic processes and response, then exploring pharmacological inhibition and pre-clinical validation studies of candidate targeted agents, and finally, summarizing the progression of those candidates in the clinic.

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“…While the relative radiosensitivity of HPV‐positive HNSCC has largely been attributed to tumor‐intrinsic factors as discussed above, immunogenic mechanisms for radiosensitivity have also been postulated 130,131 . Several studies have shown a potent adaptive immune response triggered by HPV antigens, accompanied by increased TILs which are associated with more favorable outcomes in HNSCC 132–140 .…”

Section: Crosstalk Between the Immune System Chemoradiation And Atr Inhibition In Hnsccmentioning

confidence: 99%

Pharmacologic inhibition of ataxia telangiectasia and Rad3‐related (ATR) in the treatment of head and neck squamous cell carcinoma

Karukonda

Odhiambo

Mowery

2021

Molecular Carcinogenesis

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Head and neck squamous cell carcinoma (HNSCC) poses significant treatment challenges, with high recurrence rates for locally advanced disease despite aggressive therapy typically involving a combination of surgery, radiation therapy, and/or chemotherapy. HNSCCs commonly exhibit reduced or absent TP53 function due to genomic alterations or human papillomavirus (HPV) infection, leading to dependence on the S‐ and G2/M checkpoints for cell cycle regulation. Both of these checkpoints are activated by Ataxia Telangiectasia and Rad3‐related (ATR), which tends to be overexpressed in HNSCC relative to adjacent normal tissues and represents a potentially promising therapeutic target, particularly in combination with other treatments. ATR is a DNA damage signaling kinase that is activated in response to replication stress and single‐stranded DNA breaks, such as those induced by radiation therapy and certain chemotherapies. ATR kinase inhibitors are currently being investigated in several clinical trials as part of the management of locally advanced, recurrent, or metastatic HNSCC, along with other malignancies. In this review article, we summarize the rationale and preclinical data supporting incorporation of ATR inhibition into therapeutic regimens for HNSCC.

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Enhanced Radiation Sensitivity of Human Papillomavirus-Driven Head and Neck Cancer: Focus on Immunological Aspects

Cited by 17 publications

References 84 publications

Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges

Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges

Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review

Pharmacologic inhibition of ataxia telangiectasia and Rad3‐related (ATR) in the treatment of head and neck squamous cell carcinoma

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