Deciphering the immune landscape of head and neck squamous cell carcinoma: A single-cell transcriptomic analysis of regulatory T cell responses to PD-1 blockade therapy

by Adib Miraki Feriz, Fatemeh Bahraini, Arezou Khosrojerdi, Setareh Azarkar, Seyed Mehdi Sajjadi, Edris HosseiniGol, Mohammad Amin Honardoost, Samira Saghafi, Nicola Silvestris, Patrizia Leone, Hossein Safarpour, Vito Racanelli

Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the limitations of patients’ responses to immunotherapy. Here, we aimed to examine how Nivolumab affects infiltrating T_regs in the HNSCC TME. We used single-cell RNA sequencing data from eight tissues isolated from four HNSCC donors before and after Nivolumab treatment. Interestingly, the study found that T_reg counts and suppressive activity increased following Nivolumab therapy. We also discovered that changes in the CD44-SSP1 axis, NKG2C/D-HLA-E axis, and KRAS signaling may have contributed to the increase in T_reg numbers. Furthermore, our study suggests that decreasing the activity of the KRAS and Notch signaling pathways, and increasing FOXP3, CTLA-4, LAG-3, and GZMA expression, may be mechanisms that enhance the killing and suppressive capacity of T_regs. Additionally, the result of pseudo-temporal analysis of the HNSCC TME indicated that after Nivolumab therapy, the expression of certain inhibitory immune checkpoints including TIGIT, ENTPD1, and CD276 and LY9, were decreased in T_regs, while LAG-3 showed an increased expression level. The study also found that T_regs had a dense communication network with cluster two, and that certain ligand-receptor pairs, including SPP1/CD44, HLA-E/KLRC2, HLA-E/KLRK1, ANXA1/FPR3, and CXCL9/FCGR2A, had notable changes after the therapy. These changes in gene expression and cell interactions may have implications for the role of T_regs in the TME and in response to Nivolumab therapy.

Non-financial access to healthcare services in rural areas: A case study of people with disabilities living in Northern Iran

by Lida Shams, Tahere Darvish, Mohamad Meskarpour Amiri, Sayyed-Morteza Hosseini-Shokouh, Taha Nasiri

Introduction

Access to healthcare for persons with disabilities (PWDs) is an important but often ignored issue for achieving universal health coverage. The current study aimed to investigate PWDs’ access to healthcare in the rural areas in north of Iran.

Methods

Following a descriptive-analytical design, 471 persons with disabilities (PWDs) living in the Nor city, Mazandaran province, were selected using quota sampling. Data were collected by a valid and reliable questionnaire that contained dimensions of time, geography, physical, and acceptability using face-to-face interviews. The findings are provided by central and dispersion indicators and analyses are performed with linear Regression using SPSS version 17.

Results

PWDs had moderate access to healthcare services in all dimensions. The regression models for access to health services in all four dimensions were significant (p Conclusion

A small percentage of PWDs had high access to health services. Hence, improving their access to healthcare services, particularly in rural and less developed areas, and developing appropriate policies should be the focus of Iranian policy-makers.