PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

Hong, Angela; Vilain, Ricardo E.; Romanes, Sarah Elizabeth; Yang, Yee Hwa; Smith, Elizabeth; Jones, D. Brian; Scolyer, Richard A.; Lee, C Soon; Zhang, Mei; Rose, Barbara

doi:10.18632/oncotarget.12776

Cited by 44 publications

(44 citation statements)

References 33 publications

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“… Importantly, in this study, we showed that HPV‐positive tumors have higher numbers of CD4+ and CD8+ cells both in the tumor and in the surrounding stroma, which might explain the higher expression of HLA‐II, both HLA‐DRA and HLA‐DP/DQ/DR, on tumor cells compared to HPV‐negative tumors. As previously observed, a positive correlation between PD‐L1 expression on immune cells and longer OS was found.…”

Section: Discussionsupporting

confidence: 88%

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

et al. 2018

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Background Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is a highly immunogenic tumor and differences in tumor microenvironment might contribute to the improved survival of HPV‐positive OPSCC patient. Methods A comprehensive multivariate analysis with clinical and immune variables (human leukocyte antigen [HLA] I/II, programmed death ligand 1 (PD‐L1), programmed death receptor 1 (PD1), T cells, and macrophages) was performed in 142 OPSCC patients. Results We found an inverse correlation between the expression of HLA class II molecules on tumor cells and CD68+ CD163+ tumor‐associated macrophages (TAMs). High HLA‐DP/DQ/DR expression and low number of TAMs were associated with longer disease‐specific survival and disease‐free survival (DFS). Furthermore, a new population of CD8+ FoxP3+ T cells was correlated with shorter DFS in multivariate analysis. Conclusions \We identified new prognostic markers for patients with oropharyngeal cancer, which can be used for selecting patients that can benefit from immunotherapy.

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Section: Discussionsupporting

confidence: 88%

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

et al. 2018

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“…Human papilloma virus (HPV)/p16positive tumors had significantly lower CXCL9 expression than HPV/p16-negative tumors. A correlation between HPV-positivity and PD-L1 expression has previously been reported in oropharyngeal cancer [63]. Due to the low number of HPV/p16-positive cancers in our study, the correlation between the virus, CXCL9, and PD-L1 expression in oral cancer needs validation in a study with a higher amount of HPV-positive patients.…”

Section: Variablesupporting

confidence: 49%

Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma

et al. 2018

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Oral squamous cell carcinomas are associated with a poor prognosis, which may be partly due to functional impairment of the immune response. Lymphocyte recruitment to the tumor site is facilitated by high-endothelial venules, whereas expression of programmed-death ligand 1 (PD-L1) can impair T-cell function. Thus, we hypothesize that these factors are important in shaping the immune response in oral squamous cell carcinoma. In the present study, we characterized the immune infiltrate in formalin-fixed, paraffin-embedded tumor samples from 75 oral squamous cell carcinoma patients. We used immunohistochemistry to determine the distribution of immune cell subsets, high-endothelial venules, and PD-L1, as well as quantitative real-time polymerase chain reaction to assess the expression of inflammatory cytokines and chemokines associated with lymphocyte trafficking. Finally, we calculated correlations between the presence of immune cell subsets, the gene expression patterns, high-endothelial venules, PD-L1, and the clinicopathological parameters, including patient survival. The presence of high-endothelial venules correlated with increased number of CD3+ T cells and CD20+ B cells, higher levels of the chemokines CXCL12 and CCL21, and lower levels of CCL20, irrespective of the tumors' T stage. In univariate analysis, high levels of CD20+ B cells and CD68+ macrophages, positive high-endothelial venule status, and low T and N stages predicted longer patient survival. However, only the presence of high-endothelial venules and a low T stage were independent positive prognosticators. This indicates that high-endothelial venules are important mediators and a convenient marker of an antitumor immune response in oral squamous cell carcinoma. Our findings suggest that these vessels are a potential immunomodulatory target in this type of cancer. PD-L1 staining in tumor cells correlated with lower T stage, increased infiltration of CD4+ cells, and higher expression of several inflammation-related cytokines. Thus, oral squamous cell carcinomas rich in CD4+ cells may preferentially respond to PD-1/PD-L1 blockade therapy.

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“…Cancer immunotherapy, which differs from traditional cytotoxic therapies and targeted therapies, is a new class of anti-cancer drugs with promising clinical activity in different types of tumors [ 18 , 42 - 45 ]. Previous studies have reported that pemetrexed-based chemotherapy in anaplastic lymphoma kinase rearrangement patients was associated with a higher response rate and longer PFS [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression indicates favorable prognosis for advanced lung adenocarcinoma patients treated with pemetrexed

Zhang

Bao

et al. 2017

Oncotarget

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Conventional chemotherapy for lung cancer exerts anti-tumor effects through cytotoxicity, and through immunologic regulation by reducing specific T cell subsets and inducing the expression of programmed death ligand 1 (PD-L1) on tumor cells. Even though pemetrexed has shown huge potential in combination with other targeted or immune therapies, there is still little information about the values of specific immune checkpoint markers for advanced lung adenocarcinoma treated with pemetrexed. In the present study, a total of 56 patients with advanced lung adenocarcinoma, who received pemetrexed-based chemotherapy, were included retrospectively. Immunohistochemistry was performed to assess PD-L1, programmed death 1 (PD-1), thymidylate synthase, and tumor infiltrating lymphocytes (TILs). In this cohort, the positive expression of PD-L1 and PD-1 were 26.8% and 33.9% respectively. PD-L1, PD-1, and thymidylate synthase expression were not significantly associated with any clinical features, while the expression of both PD-L1 and PD-1 were correlated with Ki-67 expression. Furthermore, the expression of PD-1 was significantly correlated with TILs. The progression-free survival (PFS) in patients with PD-L1+ specimens was significantly longer compared to PD-L1− specimens. Moreover, PD-L1 expression was an independent protective factor for PFS, and the smoking status was an independent risk factor. PD-L1 expression was significantly associated with better prognosis for patients with pemetrexed-based treatment. Our findings suggested that PD-L1 expression might be a favorable prognostic biomarker for pemetrexed-based regimen, which is a rationale for combining immunotherapy with chemotherapy for lung cancer.

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PD-L1 expression in tonsillar cancer is associated with human papillomavirus positivity and improved survival: implications for anti-PD1 clinical trials

Cited by 44 publications

References 33 publications

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer

Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma

PD-L1 expression indicates favorable prognosis for advanced lung adenocarcinoma patients treated with pemetrexed

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