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

Aarstad, Hans Jørgen; Vintermyr, Olav Karsten; Ulvestad, Elling; Kross, Kenneth W.; Heimdal, John‐Helge

doi:10.1111/apm.12356

Cited by 14 publications

(19 citation statements)

References 32 publications

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“…the MNP system, and the adaptive immune system are independently affected by the cancer disease. We have previously shown the same to be the case with stimulated monocyte MCP-1 secretion combined with T lymphocyte CD69 expression [13]. For this reason, several individual lines of measurement show similar results.…”

Section: Discussionsupporting

confidence: 67%

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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Section: Discussionsupporting

confidence: 67%

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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“…In particular, patients with evidence of a high functioning in both the adaptive and natural immune systems had a serious prognosis. Similar results were obtained with monocyte chemo‐attractant protein (MCP)‐1 secretion and the percentage of CD69‐positive lymphocyte analyses . As stimulated by LPS, HNSCC monocyte function is therefore known to predict prognosis, and in the current study we aim to investigate monocyte function upon cancer‐associated stimuli.…”

Section: Introductionsupporting

confidence: 69%

“…Several authors have shown that the functional status of the immune system is related to the prognosis of HNSCC . Furthermore, the immune system participates in the eradication of HPV‐positive (+) tumour cells during radiotherapy and also presumably so among HPV‐negative (−) patients.…”

Section: Introductionmentioning

confidence: 99%

In vitro Monocyte IL‐6 Secretion Levels Following Stimulation with Autologous Spheroids Derived from Tumour or Benign Mucosa Predict Long‐term Survival in Head and Neck Squamous Cell Carcinoma Patients

et al. 2017

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MCP-1/IL-6 in vitro monocyte secretion upon coculture with autologous fragment spheroids was studied in relation to patient 5- and 10-year overall survival rates in head and neck squamous cell carcinoma (HNSCC) patients (n = 65) diagnosed between 1998 and 2005, nine of whom had an human papilloma virus (HPV) tumour infection. The spheroids were harvested from malignant or benign tissue during primary surgery. Two weeks following surgery, freshly isolated autologous monocytes and benign or malignant spheroids were cocultured 24 h in vitro. The IL-6 secretion was expressed as a fraction of the lipopolysaccharide (LPS) response from the same batch of monocytes. HPV status was obtained by employing PCR analyses of primary diagnostic blocks. IL-6/MCP-1 response levels were not found to be dependent on HPV infection status. MCP-1 secretion did not predict prognosis, nor did in vitro IL-6 monocyte background or LPS-stimulated IL-6 secretion. At 5-year observation, dichotomized IL-6 levels following monocyte coculture, with both malignant and benign spheroids, showed a strong trend towards predicting survival, that is a low monocyte malignant coculture response showed a survival of 31 ± 17 versus 58 ± 17% with a high such response (P = 0.057). When studying monocyte IL-6 coculture responses evaluating benign and malignant spheroid results statistically together, a prediction of survival up to 10 years was found (hazard ratio = 0.48; confidence interval = 0.24-0.96; P < 0.05) with double low IL-6 responses. This survival prediction was also present after an adjustment for HPV tumour infection status. In conclusion, monocyte IL-6 in vitro secretion in cocultures with autologous spheroids/serum from HNSCCs predicted 5- and 10-year survivals, both with and without tumour HPV tumour adjustment.

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“…Oppositely, while CIBERSORT did not find a differential infiltrate related to the monocyte infiltrate in the M vs. NM cohorts, MIXTURE found that the monocyte population was significantly increased in the metastatic (M) group ( Figure 4B). This finding is supported by a previous study in HNSCC showing that patients with high monocyte frequency had lower survival with 8% 5-year overall survival (OS) compared to 65% 5-year OS for patients with low activation levels (Aarstad et al 2015). Although this study was performed on peripheral blood, it shows a link between increased monocyte activation and decreased survival in HNSCC patients.…”

Section: Pfs and Ossupporting

confidence: 83%

MIXTURE: an improved algorithm for immune tumor microenvironment estimation based on gene expression data

Fernández

Mahmoud

Veigas

et al. 2019

Preprint

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RNA sequencing has proved to be an efficient high-throughput technique to robustly characterize the presence and quantity of RNA in tumor biopsies at a given time. Importantly, it can be used to computationally estimate the composition of the tumor immune infiltrate and to infer the immunological phenotypes of those cells. Given the significant impact of anti-cancer immunotherapies and the role of the associated immune tumor microenvironment (ITME) on its prognosis and therapy response, the estimation of the immune cell-type content in the tumor is crucial for designing effective strategies to understand and treat cancer. Current digital estimation of the ITME cell mixture content can be performed using different analytical tools. However, current methods tend to overestimate the number of cell-types present in the sample, thus under-estimating true proportions, biasing the results. We developed MIXTURE, a noise-constrained recursive feature selection for support vector regression that overcomes such limitations. MIXTURE deconvolutes cell-type proportions of bulk tumor samples for both RNA microarray or RNA-Seq platforms from a leukocyte validated gene signature. We evaluated MIXTURE over simulated and benchmark data sets. It overcomes competitive methods in terms of accuracy on the true number of present cell-types and proportions estimates with increased robustness to estimation bias. It also shows superior robustness to collinearity problems. Finally, we investigated the human immune microenvironment of breast cancer, head and neck squamous cell carcinoma, and melanoma biopsies before and after anti-PD-1 immunotherapy treatment revealing associations to response to therapy which have not seen by previous methods.

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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

Cited by 14 publications

References 32 publications

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

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

In vitro Monocyte IL‐6 Secretion Levels Following Stimulation with Autologous Spheroids Derived from Tumour or Benign Mucosa Predict Long‐term Survival in Head and Neck Squamous Cell Carcinoma Patients

MIXTURE: an improved algorithm for immune tumor microenvironment estimation based on gene expression data

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