Effects of irradiation on human leukocyte antigen class I expression in human papillomavirus positive and negative base of tongue and mobile tongue squamous cell carcinoma cell lines

Haeggblom, Linnea; Nordfors, Cecilia; Tertipis, Nikolaos; Bersani, Cinzia; Ramqvist, Torbjörn; Näsman, Anders; Dalianis, Tina

doi:10.3892/ijo.2017.3916

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…One report suggests e.g. that IR increases the levels of MHC class I in HPV + OPSCC, thereby allowing for better immune recognition, while another study implies the necessity of an immune system to benefit from IR or chemotherapy (29,30). The role of CD47 has also been investigated, showing that this protein is downregulated upon IR, and that this in turn enhances immune recognition of HPV + OPSCC (31).…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation

et al. 2020

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Human papillomavirus-positive (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence and has a much better prognosis than HPV-negative (HPV -) OPSCC with radiotherapy alone, but exactly why is unknown. The present study therefore aimed to further examine the sensitivity and possible changes in gene expression of several HPV + and HPV -OPSCC, including various novel cell lines, upon ionizing irradiation (IR). Previously established HPV + UM-SCC-47, UPCI-SCC-90, CU-OP-2, CU-OP-3 and HPV -UM-SCC-4, UM-SCC-6, UM-SCC-74a, UM-SCC-19 and newly established CU-OP-17 and CU-OP-20, characterised here, were subjected to 0-6 Gy. Surviving fractions of each cell line were tested by clonogenic assays, and irregularities in cell cycle responses were examined by flow cytometry, while changes in gene expression were followed by mRNA sequencing. HPV + OPSCC cell lines showed greater variation in sensitivity to ionizing irradiation (IR) and tended to be more sensitive than HPV -OPSCC cell lines. However, their IR sensitivity was not correlated to the proportion of cells in G2 arrest, and HPVcell lines generally showed lower increases in G2 after IR. Upon IR with 2 Gy, mRNA sequencing revealed an increase in minor HPV integration sites in HPV + cell lines, and some changes in gene expression in OPSCC cell lines, but not primarily those associated with DNA repair. To conclude, HPV + OPSCC cell lines showed greater variation in their sensitivity to IR, with some that were radioresistant, but overall the HPV + OPSCC group still tended to be more sensitive to IR than the HPV -OPSCC group. In addition, HPV + OPSCC lines were more frequently in G2 as compared to HPVcell lines, but the increase in G2 arrest upon IR in HPV + OPSCC was not correlated to sensitivity to IR. Increases in minor HPV integration sites and changes in gene expression were also demonstrated after irradiation with 2 Gy.

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Section: Discussionmentioning

confidence: 99%

Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation

et al. 2020

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“…Indeed, experimentally, irradiation increased MHC class I expression in vitro in some, but not all, HPV-positive OPSCC cell lines and in one HPV-positive cell line a decrease in HPV16 E5 mRNA expression was also noted (91). Increased MHC class I expression upon irradiation could in part explain why HPV-positive tumors with absent/low MHC class I expression still respond readily to therapy and are recognized by the immune system (91). Eliciting a vigorous immune response in this context, would be in line with data obtained in mice, where HPV-positive tumors were curable after cisplatin or radiation therapy only in immunocompetent and not in immunoincompetent mice (92).…”

Section: Studies Focusing On Immunological and Stem Cell Markers In Tmentioning

confidence: 94%

“…The decrease in MHC class I expression was assumed to be due to active HPV infection and more specifically the downregulation of MHC class I by HPV E5 and E7 (23, 90). MHC class I expression was suggested to increase upon irradiation and make the tumors more sensitive to the immune system of the host (91). Indeed, experimentally, irradiation increased MHC class I expression in vitro in some, but not all, HPV-positive OPSCC cell lines and in one HPV-positive cell line a decrease in HPV16 E5 mRNA expression was also noted (91).…”

Section: Studies Focusing On Immunological and Stem Cell Markers In Tmentioning

confidence: 99%

“…MHC class I expression was suggested to increase upon irradiation and make the tumors more sensitive to the immune system of the host (91). Indeed, experimentally, irradiation increased MHC class I expression in vitro in some, but not all, HPV-positive OPSCC cell lines and in one HPV-positive cell line a decrease in HPV16 E5 mRNA expression was also noted (91). Increased MHC class I expression upon irradiation could in part explain why HPV-positive tumors with absent/low MHC class I expression still respond readily to therapy and are recognized by the immune system (91).…”

Section: Studies Focusing On Immunological and Stem Cell Markers In Tmentioning

confidence: 99%

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Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Näsman

Bersani

Lindquist

et al. 2017

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Abstract. Human papillomavirus (HPV)-positive tonsillarand base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negativeIn 2007, human papillomavirus (HPV) was recognized as a risk factor for oropharyngeal squamous cell carcinoma (OPSCC) by the International Agency for Research against Cancer (IARC), besides the traditional risk factors smoking and alcohol (1-4). Concurrently, an increased incidence of OPSCC, more specifically tonsillar and base of tongue cancer (TSCC and BOTSCC, the two main HPV-positive OPSCC sites) was described in many developed countries, and found to be due to a sharp rise of HPV-positive cases (5-18). These HPV-positive tumors had a much better clinical outcome than their HPV-negative counterparts and head and neck squamous cell carcinoma (HNSCC) in general when treated with radiotherapy and surgery (1-3, 15-17, 19, 20). Treatment of HNSCC including OPSCC has, however, gradually become more intensified with induction chemotherapy or concurrent chemo-radiotherapy and sometimes the administration of Erbitux, leading to more severe side effects (16, 20, 21). This is likely unnecessary for most HPV-positive TSCC and BOTSCC patients since they generally respond well to less therapy and furthermore, intensified therapy does not improve survival of [15][16][17] 20, 22, 23). It is, therefore, important to identify patients with HPV-positive TSCC and BOTSCC eligible for less treatment or targeted therapy and efforts focus now on finding predictive and targetable markers for these patients (24-39).Here, a short background of the field and an update on recent attempts to find predictive and targetable markers with different methodologies for individualized therapy is presented. Human Papillomavirus in Tonsillar and Base of Tongue Squamous Cell Carcinoma and an Epidemic Increase of these TumorsIn 2000, an association between HPV and OPSCC and TSCC was reported, and with radiotherapy and surgery, these HPVpositive cases had much better outcome than corresponding HPV-negative cases (80% vs. 40-50% 5-year survival) (1, 2). In 2004, a similar relationship of HPV to BOTSCC, but not to mobile tongue cancer was disclosed (40). Based on 5319

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“…It is unclear, however, whether this really has been studied extensively. Nevertheless, in vitro, it has been experimentally shown that upon irradiation, in some cases, there is an increase in MHC class I expression, while in contrast, HPV16 E5 mRNA is decreased, thereby potentially increasing the immune sensitivity of the tumors [ 102 ]. Achieving increased immune sensitivity of HPV + tumors would be favorable for the clinical outcome and in concordance with experimental data obtained in vivo [ 103 ].…”

Section: The Search Of Prognostic or Targetable Biomarkers In Hpv + And Hpv − Tscc Botscc And Opsccmentioning

confidence: 99%

Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

Näsman

Holzhauser

Kostopoulou

et al. 2021

Viruses

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The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV−) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

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Effects of irradiation on human leukocyte antigen class I expression in human papillomavirus positive and negative base of tongue and mobile tongue squamous cell carcinoma cell lines

Cited by 7 publications

References 32 publications

Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation

Sensitivity of human papillomavirus‑positive and ‑negative oropharyngeal cancer cell lines to ionizing irradiation

Human Papillomavirus and Potentially Relevant Biomarkers in Tonsillar and Base of Tongue Squamous Cell Carcinoma

Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

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