Diffuse coexpression of thyroid transcription factor-1 and p40 in a non-small cell carcinoma of the lung: Second case in the female population / Coexpresión difusa del factor de transcripción tiroidea 1 y p40 en un carcinoma de célula no pequeña del pulmón: segundo caso en la población de sexo femenino

Some non-small cell carcinomas of the lung can express TTF1 and p40 in the same tumor cells. This event has been described in only six cases prior to this one, and only in one other female. It is an extraordinary event that appears as a new entity yet to be defined. The case presented is a woman with a non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same cells. (AU)

Algunos carcinomas de célula no pequeña del pulmón pueden expresar TTF1 y p40 en las mismas células tumorales. Este evento se ha descrito únicamente en 6 casos anteriores a este, y solo en otra persona del sexo femenino. Se trata de un evento extraordinario que se muestra como una nueva entidad todavía por definir. El caso que se presenta versa sobre una mujer con un carcinoma de pulmón de célula no pequeña con coexpresión difusa en las mismas células de TTF1 y p40. (AU)

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

BACKGROUND: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. METHODS: A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. DISCUSSION: There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. TRIAL REGISTRATION: Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma.

The polycomb group (PcG) comprises a set of proteins that exert epigenetic regulatory effects and play crucial roles in diverse biological processes, ranging from pluripotency and development to carcinogenesis. Among these proteins, enhancer of zeste homolog 2 (EZH2) stands out as a catalytic component of polycomb repressive complex 2 (PRC2), which plays a role in regulating the expression of homologous (Hox) genes and initial stages of x chromosome inactivation. In numerous human cancers, including head and neck squamous cell carcinoma (HNSCC), EZH2 is frequently overexpressed or activated and has been identified as a negative prognostic factor. Notably, EZH2 emerges as a significant gene involved in regulating the STAT3/HOTAIR axis, influencing HNSCC proliferation, differentiation, and promoting metastasis by modulating related oncogenes in oral cancer. Currently, various small molecule compounds have been developed as inhibitors specifically targeting EZH2 and have gained approval for treating refractory tumors. In this review, we delve into the epigenetic regulation mediated by EZH2/PRC2 in HNSCC, with a specific focus on exploring the potential roles and mechanisms of EZH2, its crucial contribution to targeted drug therapy, and its association with cancer markers and epithelial-mesenchymal transition. Furthermore, we aim to unravel its potential as a therapeutic strategy for oral squamous cell carcinoma.

Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Cancer.

OBJECTIVE: To enhance understanding in patterns of discordance between clinical and pathological T and N staging in multiple sites of head and neck squamous cell cancer. METHODS: A retrospective cohort of 580 newly diagnosed and surgically treated head and neck squamous cell carcinoma patients from a single institution over a 10-year period are presented. Clinical and pathologic staging are compared. RESULTS: Notably, 33% of cases had staging discordance. Overall Cohen's kappa agreement was κ = 0.55 (moderate agreement). Highly discordant site stages with κ < 0.45 included: T2 oral cavity, T2 oropharynx, T3 larynx, and N1 lymph node. T2-4 oral cavity cancers were often overstaged, and more than one-third of T3 larynx cancers were understaged. Highly concordant site stages with κ>0.65 included: T1 larynx, T4 oropharynx, N0 lymph node, and N3 lymph node. CONCLUSION: There exists a quantifiable and, in certain sites, clinically relevant pattern of discordance between clinical and pathologic staging. Tumor board multidisciplinary evaluation can highlight these discrepancies and aide in limiting effects on treatment decisions. However, discordant staging can affect the interpretation and application of prognostication, treatment, and data accuracy. Further investigation is warranted to improve clinical staging accuracy in areas of highest discordance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer.

BACKGROUND: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown. METHODS: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival. RESULTS: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The combination of ENE positivity and low immune infiltration was strongly associated with poor overall survival (OS) compared to the combination of ENE positivity and high immune infiltration [hazard ratio 2.04 (95 %CI, 1.08-3.83); p = 0.024]. The immune infiltration status was not associated with OS rates in patients with ENE-negative or node negative tumors. CONCLUSION: Overall Immune infiltration at the primary site was significantly associated with clinical outcome of OSCC patients with ENE.

The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

The role of non-oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review.

INTRODUCTION: This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. RESULTS: A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. CONCLUSIONS: On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.

The novel circ_0004674/miR-139-5p/ZBTB2 regulatory cascade inhibits the development of oral squamous cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are an intriguing family of RNA molecules due to their crucial roles in the pathogenesis of oral squamous cell carcinoma (OSCC). Here, we sought to define the action of human circ_0004674 in OSCC progression. METHODS: The functional role of circ_0004674 was validated by determining its effect on cell growth, apoptosis, and tube formation ability of OSCC cells. For protein quantification, a western blot or immunohistochemistry method was applied. The interaction between miR-139-5p and circ_0004674 or zinc finger and BTB domain containing 2 (ZBTB2) was predicted by online algorithms, and their relationships were confirmed by dual-luciferase reporter and RIP assays. Xenograft models were established to uncover circ_0004674's role in tumor growth. RESULTS: Circ_0004674 expression was upregulated in OSCC. Functionally, knocking down circ_0004674 led to suppressed OSCC cell progression in vitro and delayed tumor growth in vivo. Mechanistically, circ_0004674 post-transcriptionally controlled ZBTB2 expression by competitively pairing to miR-139-5p. Furthermore, the deficiency of miR-139-5p abated circ_0004674 silencing-mediated OSCC cell progression repression, and augmentation of ZBTB2 reversed the anticancer effect of miR-139-5p on OSCC. CONCLUSION: Our findings uncover a novel regulatory cascade, the circ_0004674/miR-139-5p/ZBTB2 axis, with the ability to affect OSCC development in vitro and in vivo, providing a potential opportunity for development of OSCC therapy.

Genes involved in metastasis in oral squamous cell carcinoma: A systematic review.

Background and Aims: Oral squamous cell carcinoma is the most prevalent malignancy in the oral cavity, with a significant mortality rate. In oral squamous cell carcinoma patients, the survival rate could decrease because of delayed diagnosis. Thus, prevention, early diagnosis, and appropriate treatment can effectively increase the survival rate in patients. In this systematic review, we discussed the role of different genes in oral squamous cell carcinoma metastasis. Herein, we aimed to summarize clinical results, regarding the potential genes that promote oral squamous cell carcinoma metastasis. Methods: This systematic review was carried out under the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. An electronic search for all relevant articles published in English between January 2018 and April 2022 was performed using Scopus, PubMed, and Google Scholar search engines. All original studies published in English were included, and we excluded studies that were in a non-English language. Results: A total of 4682 articles were found, of which 14 were relevant and detected significant genes in oral squamous cell carcinoma progression. These findings investigated the overexpression of interferon-induced proteins with tetratricopeptide repeats 1 and 3 (IFIT1, IFT3), high-mobility group A2 (HMGA2), transformed growth factor-beta-induced, lectin galactoside-binding soluble 3 binding protein (LGALS3BP), bromodomain containing 4, COP9 signaling complex 6, heterogeneous nuclear ribonucleoproteins A2B1 (HNRNPA2B1), 5'-3' exoribonuclease 2 (XRN2), cystatin-A (CSTA), fibroblast growth factors 8 (FGF8), forkhead box P3, cadherin-3, also known as P-cadherin and Wnt family member 5A, ubiquitin-specific-processing protease 7, and retinoic acid receptor responder protein 2 genes lead to promote metastasis in oral squamous cell carcinoma. Overexpression of some genes (IFIT1, 3, LGALS3BP, HMGA2, HNRNPA2B1, XRN2, CSTA, and FGF8) was proven to be correlated with poor survival rates in oral squamous cell carcinoma patients. Conclusion: Studies suggest that metastatic genes indicate a poor prognosis for oral squamous cell carcinoma patients. Detecting these metastatic genes in oral squamous cell carcinoma patients may be of predictive value and can also facilitate assessing oral squamous cell carcinoma development and its response to treatment.

Impact of coconut kernel extract on carcinogen-induced skin cancer model: Oxidative stress, C-MYC proto-oncogene and tumor formation.

This study aimed at analysing the effects of coconut (Cocos nucifera L.) kernel extract (CKE) on oxidative stress, C-MYC proto-oncogene, and tumour formation in a skin cancer model. Tumorigenesis was induced by dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA). In vitro antioxidant activity of CKE was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), total phenolic and flavonoid content assays. CKE showed a higher antioxidant activity then ascorbic acid (*P < 0.05, ****P < 0.0001). HPLC and NMR study of the CKE revealed the presence of lauric acid (LA). Following the characterization of CKE, mice were randomly assigned to receive DMBA/TPA Induction and CKE treatment at different doses (50, 100, and 200 mg/kg) of body weight. LA 100 mg/kg of body weight used as standard. Significantly, the CKE200 and control groups' mice did not develop tumors; however, the CKE100 and CKE50 treated groups did develop tumors less frequently than the DMBA/TPA-treated mice. Histopathological analysis revealed that the epidermal layer in DMBA-induced mice was thicker and had squamous pearls along with a hyperplasia/dysplasia lesion, indicating skin squamous cell carcinoma (SCC), whereas the epidermal layers in CKE200-treated and control mice were normal. Additionally, the CKE treatment demonstrated a significant stimulatory effect on the activities of reactive oxygen species (ROS), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), as well as an inhibitory effect on lipid peroxidase (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) and c-MYC protein expression (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

Elective neck dissection versus elective neck irradiation in cT3/4N0 maxillary sinus squamous cell carcinoma: a propensity score matching analysis.

BACKGROUND: Maxillary sinus squamous cell carcinoma (MS-SCC) is an infrequent malignancy, and determining the optimal neck management for patients with cT3/4N0 MS-SCC remains a topic of ongoing debate. The purpose of this study was to compare the prognoses and quality of life outcomes of patients who underwent either elective neck dissection (END) or elective neck irradiation (ENI) for cT3/4N0 MS-SCC. METHODS: In this retrospective study, we enrolled patients with surgically treated cT3/4N0 MS-SCC, and the impact of different neck management strategies on regional control and disease-specific survival was compared using propensity score matching. The effect of surgical intervention on quality of life was evaluated using the Mann-Whitney U test. RESULTS: Of the 120 patients included, 36 underwent END. After propensity score matching, our analysis indicated that END did not lead to superior outcomes than ENI, as demonstrated by comparable rates of regional control (p = 0.990) and disease-specific survival (p = 0.999). However, in the 70 returned questionnaires, patients who underwent END reported higher scores in the domains of appearance, chewing, and speech than did patients who underwent ENI. CONCLUSIONS: Our findings suggest that while END and ENI contribute to similar prognoses, END yields superior functional outcomes.

Giant major aphtha.

Major aphthae are usually located on the dorsum of the tongue, the mucosal surface of the lips and the palate. They are large, round or oval ulcers, with a whitish-grey bed, well-defined borders and erythematous halo. They are very often accompanied by severe pain. Major aphthae can take up to four months to heal, often with a scar. Relapses are possible. We present a case of giant major aphtha that was previously diagnosed as squamous cell carcinoma.

A case of grade 3 squamous cell carcinoma successfully treated with methotrexate.

Cutaneous squamous cell carcinoma (cSCC) is a non-melanoma skin cancer whose lesions mostly arise on light-exposed sites. Patients with compromised immunity, Fitzpatrick I or II skin phototype, and previous burn scars or radiations are more at risk of developing it. The treatment of choice for cSCC is surgery; however nonsurgical options are generally reserved for patients who refuse a very invasive treatment or cannot tolerate a surgical procedure. We report a case of cSCC successfully treated with intralesional methotrexate.

Improved recurrence rates and progression-free survival in primarily surgically treated oral squamous cell carcinoma - results from a German tertiary medical center.

OBJECTIVES: This study aimed to explore survival and recurrence patterns in patients undergoing primarily surgical treatment for oral squamous cell carcinoma (OSCC) at a high-volume tertiary medical center in Germany. MATERIALS AND METHODS: The study included 421 patients with primary OSCC who underwent radical tumor resection, neck dissection, and reconstruction with a free flap. Prognostic relevance of clinicopathological characteristics was assessed using Cox proportional-hazards models. Kaplan-Meier method estimated local recurrence-free survival, progression-free survival (PFS), and overall survival (OS), while the log-rank test compared survival outcomes between groups. RESULTS: Recurrence manifested in 16.63% of the patients (70 patients), encompassing local recurrence in 54 patients (77.14%) and distant metastasis in 24 patients (34.28%). Neck recurrence occurred in only 1 patient (0.24%) on the contralateral side. The majority of recurrences occurred within the initial twelve months following primary tumor surgery (64.29%). Overall, the 5-year OS stood at 58.29%, while the 5-year PFS reached 72.53%. Patients with early recurrence within ≤ 12 months showed the least favorable prognosis (log-rank, all p < 0.001). CONCLUSIONS: Our findings show a significant decrease in recurrence rates and enhanced PFS at a high-volume tertiary medical center in Germany compared to previous studies. Local recurrence was the primary form observed, with most recurrences happening within the initial twelve months post-surgery. Opting for treatment at a high-volume center and devising therapy plans in interdisciplinary tumor boards may not only enhance OS but also contribute to improved PFS. CLINICAL RELEVANCE: These findings offer valuable insights for physicians regarding the post-treatment care of patients with OSCC. The results underscore the importance of frequent follow-up appointments, particularly during the initial year, and highlight the critical need for vigilance in monitoring for local recurrence.

Multi-omics analysis of immune-related microbiome and prognostic model in head and neck squamous cell carcinoma.

OBJECTIVES: The aim of our study is to explore the transcriptional and microbial characteristics of head and neck cancer's immune phenotypes using a multi-omics approach. MATERIALS AND METHODS: Employing TCGA data, we analyzed head and neck squamous cell carcinoma (HNSCC) immune cells with CIBERSORT and identified differentially expressed genes using DESeq2. Microbial profiles, obtained from the TCMA database, were analyzed using LEfSe algorithm to identify differential microbes in immune cell infiltration (ICI) subgroups. Random Forest algorithm and deep neural network (DNN) were employed to select microbial features and developed a prognosis model. RESULTS: We categorized HNSCC into three immune subtypes, finding ICI-2 with the worst prognosis and distinct microbial diversity. Our immune-related microbiome (IRM) model outperformed the TNM staging model in predicting survival, linking higher IRM model scores with poorer prognosis, and demonstrating clinical utility over TNM staging. Patients categorized as low-risk by the IRM model showed higher sensitivity to cisplatin and sorafenib treatments. CONCLUSIONS: This study offers a comprehensive exploration of the ICI landscape in HNSCC. We provide a detailed scenario of immune regulation in HNSCC and report a correlation between differing ICI patterns, intratumor microbiome, and prognosis. This research aids in identifying prime candidates for optimizing treatment strategies in HNSCC. CLINICAL RELEVANCE: This study revealed the microbial signatures associated with immunophenotyping of HNSCC and further found the microbial signatures associated with prognosis. The prognostic model based on IRM microbes is helpful for early prediction of patient prognosis and assisting clinical decision-making.

Implications of ZNF334 gene in lymph node metastasis of lung SCC: potential bypassing of cellular senescence.

BACKGROUND: The primary goal of this work is to identify biomarkers associated with lung squamous cell carcinoma and assess their potential for early detection of lymph node metastasis. METHODS: This study investigated gene expression in lymph node metastasis of lung squamous cell carcinoma using data from the Cancer Genome Atlas and R software. Protein-protein interaction networks, hub genes, and enriched pathways were analyzed. ZNF334 and TINAGL1, two less explored genes, were further examined through in vitro, ex vivo, and in vivo experiments to validate the findings from bioinformatics analyses. The role of ZNF334 and TINAGL1 in senescence induction was assessed after H2O2 and UV induced senescence phenotype determined using ß-galactosidase activity and cell cycle status assay. RESULTS: We identified a total of 611 up- and 339 down-regulated lung squamous cell carcinoma lymph node metastasis-associated genes (FDR < 0.05). Pathway enrichment analysis highlighted the central respiratory pathway within mitochondria for the subnet genes and the nuclear DNA-directed RNA polymerases for the hub genes. Significantly down regulation of ZNF334 gene was associated with malignancy lymph node progression and senescence induction has significantly altered ZNF334 expression (with consistency in bioinformatics, in vitro, ex vivo, and in vivo results). Deregulation of TINAGL1 expression with inconsistency in bioinformatics, in vitro (different types of lung squamous cancer cell lines), ex vivo, and in vivo results, was also associated with malignancy lymph node progression and altered in senescence phenotype. CONCLUSIONS: ZNF334 is a highly generalizable gene to lymph node metastasis of lung squamous cell carcinoma and its expression alter certainly under senescence conditions.

Diffuse coexpression of thyroid transcription factor-1 and p40 in a non-small cell carcinoma of the lung: Second case in the female population.

Some non-small cell carcinomas of the lung can express TTF1 and p40 in the same tumor cells. This event has been described in only six cases prior to this one, and only in one other female. It is an extraordinary event that appears as a new entity yet to be defined. The case presented is a woman with a non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same cells.

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain­containing protein 4) is a chromatin­associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, migration and drug resistance. To address the roles of BRD4 in cancer, several drugs that specifically target BRD4 have been developed. Inhibition of BRD4 has shown promising results in preclinical models, with several BRD4 inhibitors undergoing clinical trials for the treatment of various cancers. Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of cancers, remains a health challenge with a high incidence rate and poor prognosis. Conventional therapies for HNSCC often cause adverse effects to the patients. Targeting BRD4, therefore, represents a promising strategy to sensitize HNSCC to chemo­ and radiotherapy allowing de­intensification of the current therapeutic regime and subsequent reduced side effects. However, further studies are required to fully understand the underlying mechanisms of action of BRD4 in HNSCC in order to determine the optimal dosing and administration of BRD4­targeted drugs for the treatment of patients with HNSCC.

Development of a Novel Prognostic Model for Esophageal Squamous Cell Carcinoma: Insights into Immune Cell Interactions and Drug Sensitivity.

Esophageal squamous cell carcinoma (ESCC) presents a five-year survival rate below 20%, underscoring the need for improved prognostic markers. Our study analyzed ESCC-specific datasets to identify consistently differentially expressed genes. A Venn analysis followed by gene network interactions revealed 23 key genes, from which we built a prognostic model using the COX algorithm (p = 0.000245, 3-year AUC = 0.967). This model stratifies patients into risk groups, with high-risk individuals showing worse outcomes and lower chemotherapy sensitivity. Moreover, a link between risk scores and M2 macrophage infiltration, as well as significant correlations with immune checkpoint genes (e.g., SIGLEC15, PDCD1LG2, and HVCR2), was discovered. High-risk patients had lower Tumor Immune Dysfunction and Exclusion (TIDE) values, suggesting potential responsiveness to immune checkpoint blockade (ICB) therapy. Our efficient 23-gene prognostic model for ESCC indicates a dual utility in assessing prognosis and guiding therapeutic decisions, particularly in the context of ICB therapy for high-risk patients.

Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy.

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.