Mononuclear phagocytes in head and neck squamous cell carcinoma

Kross, Kenneth W.; Heimdal, John‐Helge; Aarstad, Hans Jørgen

doi:10.1007/s00405-009-1153-y

Cited by 13 publications

(16 citation statements)

References 97 publications

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“…It is possible that the shown CD69 T lymphocyte survival prediction is related to an increased level of T reg suppressor cells (32) suggesting that suppression of the specific immune system indicate decreased survival. Chronic inflammation, where macrophages play an important role, mostly promote tumor growth (7). The monocyte activation prognostic results are in accordance with other findings among HNSCC patients.…”

Section: Discussionsupporting

confidence: 90%

“…Functional changes of the peripheral blood T lymphocyte system in patients with HNSCC cancer may predict prognosis . In line with this, we have shown previously that a high percentage of T lymphocytes carrying the activation epitopes CD25, CD69, CD71, and/or HLA‐DR as measured by flow cytometry, signals impaired disease‐specific prognosis .…”

supporting

confidence: 65%

“…Many different carcinoma diseases rising from the aero‐digestive tract are suggested to be partly dependent on inflammation, e.g., HN , lung and gastro‐intestinal cancer . Mononuclear phagocytes (MNP) are important parts of both the natural immune system and in general inflammation .…”

Section: Discussionmentioning

confidence: 99%

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Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients

Aarstad

Vintermyr

Ulvestad

et al. 2015

APMIS

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This study was performed to determine whether peripheral blood (PB) monocyte and/or lymphocyte activation at diagnosis were associated with long-term prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to what extent such prognostic properties relate to human papilloma virus (HPV)-associated tumor infection of the included patients. This was a long-term prospective study describing patient survival in relation to PB T lymphocyte and monocyte activation in patients observed for up to 14 years following diagnosis. Sixty-four patients from a consecutive cohort of newly diagnosed HNSCC patients along with 16 non-cancer control patients were included over a period of almost 2 years. Monocyte responsiveness was assessed at diagnosis (N = 56 HNSCC/16 non-cancer controls) by measuring net levels of spontaneous vs lipopolysaccharide-induced monocyte chemotactic protein (MCP)-1 secretion in vitro. PB T lymphocyte activation was determined (N = 58 HNSCC/16 controls) by measuring the percentage of T cells expressing CD69 by flow cytometry. Whether HPV infection or not was determined by PCR analysis on formalin fixed paraffin-embedded tumor tissue. Tumor HPV-positive patients had better prognosis than HPV-negative patients. A low net MCP-1 response in monocytes predicted increased survival (Relative risk (RR) = 2.1; Confidence interval (CI): 1.1-4.0; p < 0.05). A low percentage of CD69 positive T lymphocytes also predicted better prognosis (RR = 2.6; CI: 1.3-5.0; p = 0.005). The predictive power of MCP-1 monocyte and CD69 T lymphocyte measures were retained when adjusted for age and gender of the patients and shown to be independent of each other (N = 50 HNSCC/16 controls). The results were similar in HPV tumor-positive and -negative patients. Patients with high monocyte- and/or T lymphocyte activation status had low survival with 8% 5 year overall survival (OS) compared to 65% 5 year OS for patients with dual low activation levels (RR = 0.27; CI: 0.14-0.56; p < 0.001), mostly secondary to disease-specific survival. Both tumor HPV-positive and -negative HNSCC patients with high percentage of CD69 positive T lymphocytes and/or high monocyte MCP-1 secretion had low long-term survival. The data suggest that the general inflammatory and adaptive immune systems are independently linked to the clinical aggressiveness of both tumor HPV-negative and -positive HNSCC patients.

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 65%

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Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients

Aarstad

Vintermyr

Ulvestad

et al. 2015

APMIS

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“…Chronic inflammation has also been suggested to promote head and neck squamous cell carcinoma (HNSCC) [4]. Furthermore, the steadily growing knowledge about the human papilloma virus (HPV) as a pathogen of some HNSCC tumors [5], especially the oropharyngeal (OP)SCC [6, 7], should encourage the addressing of inflammation in the development of HNSCC.…”

Section: Introductionmentioning

confidence: 99%

In Vitro-Stimulated IL-6 Monocyte Secretion and In Vivo Peripheral Blood T Lymphocyte Activation Uniquely Predicted 15-Year Survival in Patients with Head and Neck Squamous Cell Carcinoma

et al. 2015

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The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs.

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“…However, developments over the last 20 years have changed this perception, and a number of new immunotherapeutic approaches are being evaluated, including anti-tumor vaccines [1–6]. Although more than 1,600 tumor-associated candidate antigens are known, major challenges remain in overcoming not only the selection of tumor antigen and vaccine formulation but a variety of immunologic disturbances existing in HNSCC patients and involving tumor-derived immunosuppressive factors, host-derived suppressor cells, defective antigen processing cells, and functionally impaired T cells [3, 6–9]. The challenge in HNSCC is to overcome tumor- or host-derived immunosuppression and simultaneously restore or enhance anti-tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen

Berinstein¹,

Wolf

Naylor³

et al. 2011

Cancer Immunol Immunother

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Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

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Mononuclear phagocytes in head and neck squamous cell carcinoma

Cited by 13 publications

References 97 publications

Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients

Peripheral blood monocyte and T‐lymphocyte activation levels at diagnosis predict long‐term survival in head and neck squamous cell carcinoma patients

In Vitro-Stimulated IL-6 Monocyte Secretion and In Vivo Peripheral Blood T Lymphocyte Activation Uniquely Predicted 15-Year Survival in Patients with Head and Neck Squamous Cell Carcinoma

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen

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