Spectral Clustering of Microarray Data Elucidates the Roles of Microenvironment Remodeling and Immune Responses in Survival of Head and Neck Squamous Cell Carcinoma

Thurlow, Johanna; Murillo, Claudia L Peña; Hunter, Keith D.; Buffa, Francesca M.; Patiar, Shalini; Betts, Guy; West, Catharine M L; Harris, Adrian L.; Parkinson, Eric K.; Harrison, Paul R.; Ozanne, Brad; Partridge, M; Kalna, Gabriela

doi:10.1200/jco.2009.24.8724

Cited by 71 publications

(71 citation statements)

References 39 publications

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“…So far, the data on TIL in HNSCC was limited to the quantification and phenotyping of tumor infiltrating immune cells by immunohistochemical studies and microarray. 6,33,34 We now show that such infiltrating immune cells comprise functionally different T-cell subsets and importantly that they are reactive to the HPV16 oncoproteins. In TIL we find different subsets of HPV16-specific T cells (Th1, Th2, CTL and Tregs) with different cytokine profiles (IL-2, IFNc, IL-5) comparable to what is found in anogenital HPV16 induced lesions.…”

Section: Discussionmentioning

confidence: 81%

“…In all cultures, both CD8þ and CD4þ T cells grew out (CD4/CD8 ratio median 2.45, average 5.1 and range 0. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The composition of T cells was not clearly influenced by the culture conditions (Fig.…”

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

“…5 P53 overexpression in tumor tissue; NT¼Not Tested, þ¼ overexpression in <25% of tumorcells, þþ¼ overexpression in 26-75% of tumorcells, þþþ¼ overexpression in > 75% of cells. 6 Lymphocyte stimulation test of PBMC; NT¼Not Tested, -¼no response to HPV, HPV16 ¼ proliferation on peptides of the E6 or E7 protein. 7 Stimulation index of (5).…”

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

“…2 Patients with HPV-induced HNCSCC often present with advanced disease but their prognosis is better than HNCSCC associated with smoking and drinking. [3][4][5] Notably, the majority but not all patients with an HPVþ tumor display a strong gene signature for adaptive immune response in their tumor 6 as well as strong tumor infiltration by T cells 4 suggesting that the presence of HPV may be related to an enhanced local tumor-specific T-cell response.…”

mentioning

confidence: 99%

“…[21][22][23] There is a strong notion that the presence and type of preexisting circulating and local tumor-specific immunity influences the clinical outcome as well as that of immunotherapeutic approaches. 6,18 Thus, to optimize immune resistance to HNSCC, a better understanding of the character and specificity of tumor-infiltrating-lymphocytes (TIL) in HNSCC is needed. Therefore, an explorative study was performed in which the blood of 50 patients and 20 successfully obtained T-cell cultures from their tumors and/or lymph nodes were studied for the presence, type and function of HPV-or p53-specific T cells.…”

mentioning

confidence: 99%

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Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Heusinkveld

Goedemans

Briët

et al. 2011

Intl Journal of Cancer

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Squamous cell carcinomas of the head and neck (HNSCC), in particular those of the oropharynx, can be caused by human papilloma virus Type 16 (HPV16). Whereas these HPV-induced oropharyngeal carcinomas may express the HPV16 E6 and E7 oncoproteins and are associated with better survival, the nonvirally induced HNSCC are associated with overexpression of p53. In this study we assessed the presence of systemic and local T cells reactive against these oncoproteins in HNSCC. An exploratory study on the presence, type and function of HPV16-and/or p53-specific T cells in the blood, tumor and/or metastatic lymph node as measured by several immune assays was performed in an unselected group of 50 patients with HNSCC. Tumor tissue was tested for HPV DNA and the overexpression of p53 protein. Almost all HPV161 tumors were located in the oropharynx. Circulating HPV16-and p53-specific T cells were found in 17/47 and 7/45 tested patients. T cells were isolated from tumor cultures and/or lymph nodes of 20 patients. HPV16-specific T cells were detected in six of eight HPV1 tumors, but in none of the 12 HPV-tumors. Tumor-infiltrating p53-specific T cells were not detected. In depth analysis of the HPV16-specific T-cell response revealed that this response comprised a broad repertoire of CD41 T-helper Type 1 and 2 cells, CD41 regulatory T cells and CD81 T cells reactive to HPV16. The local presence of HPV16-specific T-cell immunity in HPV16-induced HNSCC implicates a role in the antitumor response and support the development of immunotherapy for HNSCC.

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Section: Discussionmentioning

confidence: 81%

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Heusinkveld

Goedemans

Briët

et al. 2011

Intl Journal of Cancer

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HighRAB25expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

et al. 2013

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Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment.

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Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma

Kao

Armstrong

Condon

et al. 2011

Cancer

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Functional polynorbornenes (PNBEs) containing pyrrolidine moiety and bis(trifluoromethyl)biphenyl side group were synthesized via ring‐opening metathesis polymerization (ROMP), and the microstructure of polymer chain was characterized by NMR spectroscopy. Poly(N‐3,5‐bis(trifluoromethyl)biphenyl‐norbornene‐pyrrolidine) (PTNP) and poly(N‐phenyl‐norbornene‐pyrrolidine) (PPNP) are supposed to have practically trans double bonds and adopt isotactic syn conformation, whereas poly(N‐3,5‐bis(trifluoromethyl)biphenyl‐norbornene‐dicarboximide) (PTNDI) has both trans and cis double bonds and atactic microstructure. PTNP, PTNDI, and PPNP have much different dielectric constants of 20, 7, and 3, respectively, which is attributed to both the polar 3,5‐bis(trifluoromethyl)biphenyl group and the stereoregular chain structure. The existence of rigid pyrrolidine moiety has a positive contribution to form the tactic polymer chain during ROMP. Polymers are highly thermal stable up to ∼300 °C. Having good dielectric properties and thermal stability, these functional PNBEs are expected as the potential dielectric material in thin film capacitors. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

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Spectral Clustering of Microarray Data Elucidates the Roles of Microenvironment Remodeling and Immune Responses in Survival of Head and Neck Squamous Cell Carcinoma

Abstract: The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.

Cited by 71 publications

References 39 publications

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

HighRAB25expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma

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