Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma

Cho, Young-Ah; Yoon, Hye‐Jung; Lee, Jae‐Il; Hong, Sam-Pyo; Hong, Seong‐Doo

doi:10.1016/j.oraloncology.2011.08.007

Cited by 207 publications

(199 citation statements)

References 18 publications

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“…showed strong trends with the development of distant metastases. The findings suggest that there may be a biologically significant role for B7-H1 expression in the development of distant metastasis, perhaps akin to the findings in numerous studies on other carcinomas [23,24,27,[32][33][34] and on melanomas [25]. In our study, this association did not carry through to a benefit in overall, disease free, or disease specific survival.…”

Section: Discussionsupporting

confidence: 86%

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Ukpo

Thorstad

Lewis

2012

Head and Neck Pathol

122

104

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Human papillomavirus (HPV) is associated with oropharyngeal squamous cell carcinomas. Persistent viral infection is postulated to lead to carcinogenesis, although infection of benign adjacent epithelium is not typically observed. It is known that immune evasive tumor cells can provide an ideal niche for a virus. The B7-H1/ PD-1 cosignaling pathway plays an important role in viral immune evasion by rendering CD8? cytotoxic T cells anergic. We hypothesized that HPV-related oropharyngeal squamous cell carcinomas express B7-H1 as a mechanism for immune evasion. A tissue microarray was utilized, for which HPV E6/E7 mRNA by in situ hybridization was previously performed. Immunohistochemistry was performed to detect B7-H1 and staining was characterized by pattern, distribution, and intensity. B7-H1 was expressed by 84 of the 181 (46.4 %) cases. Both tumor cell membranous and cytoplasmic expression were present and cytoplasmic expression was identified in some peritumoral lymphocytes. Expression was analyzed in several different ways and then considered binarily as positive versus negative. Tumors expressing B7-H1 were more likely to be HPV positive (49.2 vs. 34.1 %, p = 0.08). B7-H1 expression showed no correlation with disease recurrence in the entire cohort (OR = 1.09, p = 0.66), HPV positive cohort (OR = 0.80, p = 0.69) or HPV negative cohort (OR = 2.02, p = 0.22). However, B7-H1 expression intensity did correlate with the development of distant metastasis (p = 0.03), and B7-H1 intensity of 3? (versus all other staining) showed a strong trend towards distant metastasis in the HPV positive (OR = 6.67, p = 0.13) and HPV negative (OR = 9.0, p = 0.13) cohorts. There was no correlation between B7-H1 expression and patient survival for any of the different ways in which staining was characterized, whether binarily, by distribution, intensity, or combined scores. B7-H1 is expressed in the majority of oropharyngeal squamous cell carcinomas with transcriptionally-active HPV. This suggests that B7-H1 expression by tumor cells may play a role in harboring persistent HPV infection.

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Section: Discussionsupporting

confidence: 86%

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Ukpo

Thorstad

Lewis

2012

Head and Neck Pathol

122

104

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“…In addition to expression on tumor cells, PD-L1 can be detected on cells located in the tumor microenvironment, and high levels of PD-L1 expression have been reported in TILs and tumor-associated macrophages [49,61,62]. However, the ultimate meaning of the PD-L1 expression on tumor cells and other cells in the microenvironment remains to be fully determined.…”

Section: Pd-1/pd-l1 In Malignant Diseasesmentioning

confidence: 99%

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Merelli

Massi

Cattaneo

et al. 2014

Critical Reviews in Oncology/Hematology

154

108

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“…Lymph node-infiltrating CD8 þ T cells as well as CD20 þ B cells were also found to be prognostic in both oropharyngeal and hypopharyngeal cancers, although interestingly, infiltration of T cells into the primary disease was not found to be prognostic in this cohort (27). In oral cavity cancers, peritumoral CD8 þ T cells were found to be associated with lymph node metastases, tumor size, and clinical stage (13). Expression of immune checkpoint ligands and their receptors has also been associated with prognosis in some instances, although the data are mixed.…”

Section: Immune Reactivity and Prognosismentioning

confidence: 77%

“…Head and neck cancers not associated with HPV infection likely also co-opt immune regulatory mechanisms to facilitate their progression. Increased PD-L1 expression similarly has been detected on tobacco-and alcohol-induced SCCs of the head and neck (11,(13)(14)(15)(16), as well as other virally mediated tumors, including nasopharyngeal carcinoma and natural killer T (NKT)-cell lymphoma (17). HPV-targeted vaccination is recommended for adolescent boys and girls to prevent incident HPV infection.…”

Section: Tumor Developmentmentioning

confidence: 99%

Immunity in Head and Neck Cancer

Schoenfeld

2015

Cancer Immunology Research

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Head and neck cancers are a diverse group of malignancies that includes an increasing number of virally mediated cancers in addition to tumors caused by tobacco and alcohol use. In both cases, tumor development is intimately related to the host immune system, and the status of an endogenous antitumor response is likely prognostic. Virally mediated cancers provide unique targets for preventive vaccines that generate immune responses directed against virus-associated antigens. Once head and neck tumors develop, they are commonly treated with surgery, radiotherapy, and/or chemotherapy. These treatments are associated with significant toxicities, and despite this, subgroups of patients respond poorly and are likely to relapse and die of their disease. Tumor immunotherapy may allow for improvements in both treatment-associated toxicity and outcome. In addition to providing specific targets for therapeutic vaccines and adoptive therapy, virally associated cancers may also be particularly dependent on immune checkpoints; therefore, immune checkpoint inhibitors are being actively tested for these diseases. Cancers that are not virally mediated may also respond to immunotherapies, and biomarkers that could predict response to immunotherapy irrespective of viral status are being evaluated. Multiple ongoing studies are testing benefits of immunotherapy in the management of metastatic squamous cell carcinoma of the head and neck. Early promising results pave the way for future studies that will expand testing to nonmetastatic diseases and other types of head and neck cancers. Prospects of combining various immunotherapies and more established treatments such as chemotherapy and radiotherapy are very intriguing and may provide synergistic benefits.

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Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma

Cited by 207 publications

References 18 publications

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

B7-H1 Expression Model for Immune Evasion in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

Immunity in Head and Neck Cancer

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