Single-cell microinjection of cytochromec can result in gap junction-mediated apoptotic cell death of bystander cells in head and neck cancer

Head & Neck ◽  
2005 ◽  
Vol 27 (9) ◽  
pp. 794-800 ◽  
Author(s):  
Douglas K. Frank ◽  
Bozena Szymkowiak ◽  
Olgica Josifovska-Chopra ◽  
Torahiko Nakashima ◽  
Kathleen W. Kinnally
Keyword(s):  
Cell Death ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Gap Junction ◽  
Single Cell ◽  
Neck Cancer ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Bystander Cells

scholarly journals Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Manuela Schwegler ◽  
Anna M. Wirsing ◽  
Hannah M. Schenker ◽  
Laura Ott ◽  
Johannes M. Ries ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Tissue Sample ◽  
Apoptotic Cell ◽  
Treatment Strategies ◽  
Tissue Microarrays ◽  
Cell Internalization ◽  
Cell Structures

Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types.Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death.Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients’ survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p=0.008).Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.

scholarly journals 903 Human cancer-associated fibroblast subsets can predict immune checkpoint response in head and neck cancer patients

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A947-A947
Author(s):  
Diana Graves ◽  
Aleksandar Obradovic ◽  
Michael Korrer ◽  
Yu Wang ◽  
Sohini Roy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Single Cell ◽  
Rna Sequencing ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Single Cell Rna Sequencing

BackgroundUse of anti-PD-1 immune checkpoint inhibitors (ICI) is currently the first line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but critical work remains in identifying factors guiding resistance mechanisms.1 2 While recent studies have specifically implicated cancer-associated fibroblasts (CAFs) as potential mediators of immunotherapy response, the immunoregulatory role of CAFs in head and neck cancer has not been thoroughly explored.3–5MethodsTo determine if there are changes in cell populations associated with anti-PD-1 therapy in head and neck cancer patients, we performed high dimensional single-cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the anti-PD-1 therapy, nivolumab, for the duration of one month. Tumor specimens were analyzed pre- and post-treatment with single-cell RNA sequencing performed on 4 patients as well as bulk RNA sequencing on 40 patients. Matched scRNA-SEQ data was analyzed using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform to determine TME cells that correlated with response and resistance to nivolumab.6 For CAF functional studies, surgical tumor specimens were processed and enriched for CAF subtypes, and these were co-cultured with T cells from peripheral blood and tumor infiltrating lymphocytes.ResultsWe identified 14 distinct cell types present in HNSCC patients. Of these 14 cell types, the fibroblast subtype showed significant changes in abundance following nivolumab treatment. We identified 5 distinct clusters of cancer-associated fibroblast subsets (HNCAF-0, 1, 2, 3, and 4) of which, two clusters, HNCAF-0 and HNCAF-3 were predictive of patient response to anti-PD-1 therapy. To determine the significance of these CAF subsets’ function, we isolated HNCAF-0/3 cells from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that HNCAF-0/3 reduced TGFβ-dependent PD-1+TIM-3+ exhaustion of T cells and increased CD103+NKG2A+ resident memory phenotype and cytotoxicity to enhance overall function.ConclusionsTo our knowledge, we are the first to characterize CAF heterogeneity within the head and neck TME and show direct immunostimulatory activity of CAFs. Our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC, and we have identified clinically actionable CAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.Trial RegistrationNCT03238365ReferencesFerris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–1867.Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–965.Dominguez CX, Muller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov 2020;10:232–253.Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20212–20217.Kieffer Y, Hocine HR, Gentric G, Pelon F, Bernard C, Bourachot B, Lameiras S, Albergante L, Bonneau C, Guyard A, et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov 2020;10:1330–1351.Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH, Rathmell WK, Jonasch E, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 2021;184:2988–3005.Ethics ApprovalPatients provided informed consent for this work. All experimental procedures were approved by the Institutional Review Board of Vanderbilt University Medical Center (IRB: 171883).

scholarly journals Anti-cancer effect of Atractylodes macrocephala extract by double induction of apoptotic and autophagic cell death in head and neck cancer cells

2017 ◽  
Vol 12 (2) ◽  
pp. 25 ◽  
Author(s):  
Ni Kou ◽  
Hyejoung Cho ◽  
Hye-Eun Kim ◽  
Qiaochu Sun ◽  
Kyuhyeon Ahn ◽  
...  
Keyword(s):  
Cell Death ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Video Clip ◽  
Head And Neck Carcinoma ◽  
Autophagic Cell Death ◽  
Apoptosis Resistance ◽  
Apoptotic Pathway ◽  
Atractylodes Macrocephala

<p class="MS">The apoptosis resistance restricts the efficacy of traditional therapies of head and neck squamous cell carcinoma (HNSCC). To overcome this problem, <em>Atractylodes macrocephala</em>, a traditional Korean and Chinese herbal medicine, has been used in clinical practice. In the present study, the anticancer effect of <em>A. macrocephala</em> extract was investigated and its underlying mechanisms using head and neck cancer KB cell line. The extract-induced cytotoxicity was mediated by autophagic cell death as well as apoptosis in HNSCC cells though extrinsic apoptotic pathway and the Akt/mTOR autophagic pathway. This study suggests that <em>A. macrocephala</em> extracts can be a potential drug to overcome side effects and susceptibility for head and neck carcinoma by double induction of apoptosis and autophagy.</p><p class="MS"><strong>Video Clip of Methodology</strong>: 6 min 27 sec  <a href="https://www.youtube.com/v/iRpGT4zpfs4">Full Screen</a>    <a href="https://www.youtube.com/watch?v=iRpGT4zpfs4">If Failed</a></p>

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