Multiparametric immune profiling in HPV– oral squamous cell cancer

Feng, Zipei; Bethmann, Daniel; Kappler, Matthias; Ballesteros-Merino, Carmen; Eckert, Alexander W.; Bell, R. Bryan; Cheng, Allen; Bui, Tuan; Leidner, Rom S.; Urba, Walter J.; Johnson, Kent J.; Hoyt, Clifford; Bifulco, Carlo; Bukur, Juergen; Wickenhauser, Claudia; Seliger, Barbara; Fox, Bernard A.

doi:10.1172/jci.insight.93652

Cited by 142 publications

(171 citation statements)

References 51 publications

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“…For future studies, we aim to conduct a similar multiparameters analysis in a bigger cohort of patients to further support the relevance of our findings. Studying the spatial interaction between markers as proximity between cells will also be of additional value . In addition, differences in phenotype and functionality of immune cells found within or in proximity of the tumor and immune cells found far from the tumor could be explored.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…However, elevated levels of Treg infiltrates in tumors can accompany elevated levels of effector T cell infiltrates and thus are not absolute indicators of an overall immunosuppressive TME 42 . Recent data using advanced image analysis techniques demonstrated that the proximity of effector CD8 T cells to Tregs correlated with worse prognosis in patients with oral cancer, 43 suggesting that spatial distribution of subsets within the tumor, rather than mere presence or prevalence, may determine their immunosuppressive effect.…”

Section: Immune System and Cancermentioning

confidence: 99%

Role of the immunosuppressive microenvironment in immunotherapy

Tormoen

Crittenden

Gough

2018

Advances in Radiation Oncology

120

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Immunotherapy is reshaping cancer treatment paradigms; however, response rates to immune therapies are low and depend on the host's pre-existing antitumor immunity. The tumor microenvironment is comprised of malignant cells, stroma, and extracellular molecules and can hinder immune control of tumors. Herein, we review how anti-tumor immune responses are formed and how tumors avoid immune destruction. We also outline potential therapeutic targets in the immunosuppressive tumor microenvironment to promote immune control of tumors.

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“…12,13 These and other studies suggest that a detailed comparison of the immunological differences between HPV+ and HPV- HNSCC provides an opportunity to identify immunological determinants that contribute to successful treatment in HNSCC that may be broadly applicable to cancer treatment in general. 14–16 …”

Section: Introductionmentioning

confidence: 99%

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

et al. 2018

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Cancers progress when the immune system fails to identify and eliminate malignant cells. Recognition of this, combined with advances in tumor immunology, has allowed development of therapies that induce effective anti-tumor immune responses. For incompletely-understood reasons, effective responses to immunotherapy occur in some patients and not others. Head and neck squamous cell carcinomas (HNSCC) are a common cancer type that can be divided into two subsets based on human papillomavirus (HPV) status. HPV status is a strong predictor of positive clinical outcome. Expression of exogenous viral antigens by HPV+, but not HPV-, HNSCC allows direct comparison of the immune status (immune cell presence and characteristics) between these two otherwise anatomically-similar tumors. Using TCGA data, we compared the immune landscape between HPV+ and HPV- treatment-naïve HNSCC. As compared to HPV- samples, HPV+ HNSCC exhibited a strong Th1 response characterized by increased infiltration with multiple types of immune cells and expression of their effector molecules. HPV+ HNSCC also expressed higher levels of CD39 and multiple T-cell exhaustion markers including LAG3, PD1, TIGIT, and TIM3 compared to HPV- HNSCC. Importantly, patients with higher expression of these exhaustion markers–indicative of a T-cell-inflamed tumor–correlated with markedly improved survival in HPV+, but not HPV-, HNSCC. Thus, profound differences exist between the immune landscape of HPV+ and HPV- HNSCC. These results suggest that immune checkpoint inhibitor therapy is a promising treatment strategy for HPV+ HNSCC, and that expression of immune checkpoint molecules could serve as a predictive biomarker of patient outcome in HPV+ HNSCC.

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Multiparametric immune profiling in HPV– oral squamous cell cancer

Cited by 142 publications

References 51 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

Role of the immunosuppressive microenvironment in immunotherapy

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

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