Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

Abstract

Objective: To analyze the role of frequency of heterotypic neutrophil-in-tumor structure (FNiT) in the prognosis of patients with buccal mucosa squamous cell carcinoma (BMSCC). Methods: In vitro, we cocultured BMSCC cell line-H157 with neutrophils to form heterotypic neutrophil-in-tumor structures, which were then subject to fluorescence staining. Clinically, 145 patients were retrospectively enrolled. Associations between FNiT and clinicopathological variables including age, sex, smoking history, drinking history, betel nut chewing, tumor stage, node stage, metastasis, disease stage, lymphovascular invasion, extranodal extension, perineural invasion, and tumor grade were analyzed by chi-square test, and the main endpoints of interest were recurrence-free survival (RFS) and disease-specific survival (DSS) which were analyzed by the Kaplan-Meier method and Cox model. Results: Fluorescent staining results of typical heterotypic neutrophil-in-tumor structure showed that well-differentiated H157 cells had a stronger ability to internalize more neutrophils than poorly-differentiated H157 cells, with the latter often internalizing only one neutrophil or nothing. The mean FNiT was 4.2‰, with a range from 2.3‰ to 7.8‰. A total of 80 patients relapsed and 84 patients died of the disease. The 5-year RFS and DSS rate was 42% and 42%, respectively. Patients with an FNiT≥4.2‰ had a significantly higher risk for locoregional recurrence and cancer-caused death than those with an FNiT<4.2‰ (p=0.001 and p<0.001, respectively). The FNiT alone was independently significant in predicting poor RFS, and the FNiT along with tumor grade was an independent predictor for DSS. Conclusion: The FNiT as a novel predictor is significantly negatively associated with both the RFS and DSS of patients with BMSCC.

SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination

“…Cell-in-cell (CIC) structures, characterized by the presence of one or more viable cells inside of another cell, are a type of unique cellular structures that had been extensively documented in a wide range of human cancer tissues [ 10 , 11 ], where the presence of cell-in-cell structures was demonstrated to regulate clonal selection [ 12 ] and genome stability [ 13 , 14 ], and to profoundly impact patient outcomes as an independent prognostic factor [ 15 – 17 ]. Active intercellular interactions, controlled by a set of core elements [ 18 – 20 ], could produce CIC structures of homotypic (between same type of cells) and/or heterotypic (between different types of cells) [ 21 , 22 ], both of which generally lead to the death of internalized cells in acidified vacuoles [ 10 , 23 ].…”

AIM-CICs: automatic identification method for Cell-in-cell structures based on convolutional neural network

“…Comparing with the traditional end-to-end manner, i.e., to train a multi-class detection model with different kinds of cells marked simultaneously, our model of separated detection will achieve the flexibility for the raw samples to be recategorized and repurposed. In AIM-CICs developed in this study, the second task included a well-trained 7-category classifier (5 CICs subtypes plus one non-CICs and one F-category) to define the multiple subtypes of CIC structures, which is compatible with the cell candidates from the first step. This two-step algorithm is also advantageous in debugging the possible mechanisms leading to inferior final prediction outcomes, as each step could be optimized separately.…”

“…Cell-in-cell structures (CICs) typically referred to the unusual eukaryotic cells involving the whole objects internalized partially or completely inside of others, which had been observed in diverse physiological and pathological samples [1, 2]. The presence of CICs was reported to be correlated with patient prognosis in a group of human tumors, such as breast cancer [3], head and neck squamous carcinoma [4, 5], and pancreatic ductal adenocarcinoma [6]. Functional studies implicated CICs in a number of biomedical processes, including embryonic development [7], mitotic surveillance [8], tumor evolution [9], and immune homeostasis [10] and the forth.…”

Role and dynamics of vacuolar pH during cell-in-cell mediated death

“…Cell-in-cell structure (CICs) refers to a unique type of cellular structure characterized by the enclosure of one or more cells into the cytosolic vacuoles of another cell. CICs had been mostly documented in various of human tumors 1 , 2 , such as pancreatic cancer 3 , 4 , head and neck squamous cell carcinoma 5 , 6 , and breast cancer 7 , 8 , where it was proposed to mediate competition between tumor cells to facilitate clonal selection and tumor evolution 9 . Meanwhile, recent studies implicated CICs in a wider range of biological processes, such as embryonic development 10 , genome stability 11 , 12 , virus infection 13 , 14 , and immune homeostasis 15 , 16 and the like.…”