Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods : CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

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CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

10.21203/rs.3.rs-15782/v1 ◽

2020 ◽

Author(s):

Lei Li ◽

Pengfei Zheng

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

T Cells ◽

B Cells ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd8 T Cells ◽

Lung Squamous Cell Carcinoma ◽

Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods: CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

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CD103+ tumor-resident CD8+ T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000452 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000452 ◽

Cited By ~ 1

Author(s):

Rehana Hewavisenti ◽

Angela Ferguson ◽

Kevin Wang ◽

Deanna Jones ◽

Thomas Gebhardt ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

T Cells ◽

T Cell ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd8 T Cells ◽

Protective Immunity ◽

Oropharyngeal Squamous Cell Carcinoma ◽

The Cancer Genome Atlas

BackgroundHuman Papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing cancers in the Western world. When compared to OPSCCs induced by smoking or alcohol, patients with HPV+ OPSCC, have better survival and the mechanisms remain unclear.MethodsThe Cancer Genome Atlas (TCGA) database was examined for genes associated with tissue-resident CD8+ T cells. Multiplex immunohistochemistry (IHC) staining was performed on tumor specimen taken from 35 HPV+ and 27 HPV- OPSCC patients.ResultsTCGA database revealed that the expression of genes encoding CD103 and CD69 were significantly higher in HPV+ head and neck SCCs (HNSCC) than in HPV- HNSCC. Higher expression levels of these two genes were also associated with better overall survival. IHC staining showed that the proportion of CD103+ tumor-resident CD8+ T cells were significantly higher in HPV+ OPSCCs when compared to HPV- OPSCC. This higher level was also associated with both lower risk of loco-regional failure, and better overall survival. Importantly, patients with HPV- OPSCC who had comparable levels of CD103+ tumor-resident CD8+ T cells to those with HPV+ OPSCC demonstrated similar survival as those with HPV+OPSCC.ConclusionOur results show that CD103+ tumor-resident CD8+ T cells are critical for protective immunity in both types of OPSCCs. Our data further suggest that the enhanced local protective immunity provided by tumor-resident T cell responses is the underlying factor driving favorable clinical outcomes in HPV+ OPSCCs over HPV- OPSCCs.

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CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

10.21203/rs.3.rs-31870/v1 ◽

2020 ◽

Author(s):

Lei Li ◽

Pengchao Zheng

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

T Cells ◽

B Cells ◽

Lung Adenocarcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd8 T Cells ◽

Lung Squamous Cell Carcinoma ◽

Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods: CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5, P=0.01) and disease-free survival (DFS HR=1.4, P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS (OS HR=0.78, P=0.071) and DFS (DFS HR=1, P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

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Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-002088 ◽

2021 ◽

Vol 9 (5) ◽

pp. e002088

Author(s):

Dan P Zandberg ◽

Ashley V Menk ◽

Maria Velez ◽

Daniel Normolle ◽

Kristin DePeaux ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cd8 T Cells ◽

Oxidative Metabolism ◽

Cox Regression ◽

Tumor Hypoxia ◽

Parental Line

The majority of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC) (R/M) do not benefit from anti-PD-1 therapy. Hypoxia induced immunosuppression may be a barrier to immunotherapy. Therefore, we examined the metabolic effect of anti-PD-1 therapy in a murine MEER HNSCC model as well as intratumoral hypoxia in R/M patients. In order to characterize the tumor microenvironment in PD-1 resistance, a MEER cell line was created from the parental line that are completely resistant to anti-PD-1. These cell lines were then metabolically profiled using seahorse technology and injected into C57/BL6 mice. After tumor growth, mice were pulsed with pimonidazole and immunofluorescent imaging was performed to analyze hypoxia and T cell infiltration. To validate the preclinical results, we analyzed tissues from R/M patients (n=36) treated with anti-PD-1 mAb, via immunofluorescent imaging for number of CD8+ T cells (CD8), Tregs and the percent area (CAIX) and mean intensity (I) of carbonic anhydrase IX in tumor. We analyzed disease control rate (DCR), progression free survival (PFS), and overall survival (OS) using proportional odds and proportional hazards (Cox) regression. We found that anti-PD-1 resistant MEER has significantly higher oxidative metabolism, while there was no difference in glycolytic metabolism. Intratumoral hypoxia was significantly increased and CD8+ T cells decreased in anti-PD-1 resistant tumors compared with parental tumors in the same mouse. In R/M patients, lower tumor hypoxia by CAIX/I was significantly associated with DCR (p=0.007), PFS, and OS, and independently associated with response (p=0.028) and PFS (p=0.04) in a multivariate model including other significant immune factors. During PD-1 resistance, tumor cells developed increased oxidative metabolism leading to increased intratumoral hypoxia and a decrease in CD8+ T cells. Lower tumor hypoxia was independently associated with increased efficacy of anti-PD-1 therapy in patients with R/M HNSCC. To our knowledge this is the first analysis of the effect of hypoxia in this patient population and highlights its importance not only as a predictive biomarker but also as a potential target for therapeutic intervention.

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CD19+IL-10+ regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4+ T cells to CD4+Foxp3+ regulatory T cells

Oral Oncology ◽

10.1016/j.oraloncology.2015.11.003 ◽

2016 ◽

Vol 53 ◽

pp. 27-35 ◽

Cited By ~ 57

Author(s):

Xi Zhou ◽

Yu-Xiong Su ◽

Xiao-Mei Lao ◽

Yu-Jie Liang ◽

Gui-Qing Liao

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

B Cells ◽

Regulatory T Cells ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd4 T Cells ◽

Tongue Squamous Cell Carcinoma ◽

Regulatory B Cells

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Analysis of radiotherapy‑induced alteration of CD8+ T cells and PD‑L1 expression in patients with uterine cervical squamous cell carcinoma

Oncology Letters ◽

10.3892/ol.2021.12707 ◽

2021 ◽

Vol 21 (6) ◽

Author(s):

Yasumasa Mori ◽

Hiro Sato ◽

Takuya Kumazawa ◽

Tiara Permata ◽

Yuya Yoshimoto ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd8 T Cells ◽

Cervical Squamous Cell Carcinoma

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Orthotopic tongue squamous cell carcinoma (SCC) model exhibiting a different tumor-infiltrating T-cell status with margin-restricted CD8+ T cells and regulatory T cell-dominance, compared to skin SCC

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2020.03.022 ◽

2020 ◽

Vol 526 (1) ◽

pp. 218-224

Author(s):

Yoshihisa Kashima ◽

Naoto Nishii ◽

Hidetake Tachinami ◽

Emi Furusawa ◽

Shigenori Nagai ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

T Cell ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cd8 T Cells ◽

Regulatory T Cell ◽

Tongue Squamous Cell Carcinoma

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Potential role of botanical drug APG-157 as immune adjuvant in patients with oral squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17572 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17572-e17572

Author(s):

Daniel Sanghoon Shin ◽

Eri Srivatsan ◽

Hassan Nasser ◽

Anela Tosevska ◽

Jonathan Jacobs ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Oral Squamous Cell Carcinoma ◽

Phase I ◽

Cell Carcinoma ◽

Inflammatory Cytokines ◽

Squamous Cell ◽

Cd8 T Cells ◽

Post Treatment ◽

Rna Seq

e17572 Background: Natural botanical drugs, such as curcumin, resveratrol and related flavonoids, are under clinical studies. Previous pilot study of curcumin, a polyphenol, for normal and patients with oral squamous cell carcinoma (OSCC) showed significant inhibition of inflammatory cytokines in saliva. Phase I investigation was performed on APG-157 to evaluate the potential utility an as oral drug for the treatment of OSCC. Methods: A double-blind, randomized, placebo-controlled phase I clinical trial was conducted with a botanical preparation containing a combination of curcumin related polyphenol molecules (pharmaceutical name APG-157). 12 Subjects with oral cancer and 13 normal control subjects were recruited. Two doses of the drug, 3x100 mg and 3x200 mg, were tested. The drug was administered orally each hour for 3 consecutive hours. Blood and saliva were collected pre-treatment and 1, 2, 3, and 24 hours post-treatment. Salivary cells and supernatants were analyzed for the expression of cytokines by multiplex ELISA and microbial content by 16S RNA sequence. Pre- and post-treatment tumor biopsies of one subject were studied for expression using the RNA seq and immunofluorescence (IF). Results: This study did not reveal any toxicity and there was a dose dependent inhibition of inflammatory cytokines, IL-1β, TNF-alpha and IL-8 in the salivary supernatant of cancer subjects treated with the drug. Tumor RNA-seq revealed down regulation of gene ontologies of cell adhesion, cell cycle and cell division and up regulation of generation of precursor metabolite/energy in the post-treatment tumor sample. Microbiome study showed significant decrease in Bacterioides after 24 hours of treatment. There was also a trend of decreasing Bacteroides among other cancer subjects treated with APG-157. IF showed a marked increase in the number of CD4, CD8 T cells in post-treatment tumor. PD-L1 expression was up-regulated in the post-treatment tumor sample. Conclusions: APG-157 is found to be safe and toxicity was not observed. The drug has shown a decrease in inflammatory cytokines. Moreover, there was a markedly increased CD4, CD8 T cells infiltration on a subject and decreased Bacteriodes microbial population after APG-157 treatment suggesting that it might have potential synergistic effect with immune checkpoint blockade immunotherapy. Decreased expression of cell growth related genes and increased expression of growth inhibitory genes pointed to a potential anti-tumor activity of APG-157.

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