OBJECTIVES: To investigate the characteristics of immune cell infiltration in tumor samples from Chinese patients with clear cell renal cell carcinoma (ccRCC) and the correlation of immune cell infiltration with tumor stage and response to immunotherapy. METHODS: Tumor samples and clinicopathological data were collected from 154 ccRCC patients treated in Nanfang Hospital, Southern Medical University from October, 2020 to October, 2023. The immune cell types infiltrating the tumor tissues were identified using immunohistochemistry and immunofluorescence staining, and their correlations with the patients' clinicopathological characteristics were analyzed. Patient-derived tumor tissue fragment models (PDTF) models, constructed using tumor tissues from 22 patients, were treated with PD-1 monoclonal antibody, and T cell activation was detected using flow cytometry to assess the patients' responses to immunotherapy. RESULTS: In Chinese ccRCC patients included in this study, CD8⁺ T cells, CD4⁺ T cells, and CD3⁺ T cells were the most abundant in the tumor tissues. Higher infiltration levels of CD3⁺ T cells (P=0.004), PD-1⁺ T cells (P=0.020), CD68⁺ T cells (P=0.049), CD79⁺ T cells (P=0.049), and Tryptase⁺ cells (P=0.049) were all positively correlated with a larger tumor size (≥5 cm). A higher infiltration level of CD4⁺ T cells was associated with a lower tumor stage. Patients with higher International Society of Urological Pathology (ISUP) grades had higher infiltration levels of CD3⁺ T cells (P=0.023), CD8⁺ T cells (P=0.045), PD-1⁺ T cells (P=0.014), CD20⁺ B cells (P=0.020) and CD79⁺ B cells (P=0.049), and lower levels of Tryptase⁺ cells (P=0.001). Patients with abundant infiltrating immune cells tended to have better responses to immunotherapy. CONCLUSIONS The infiltrating immune cells are heterogeneous in Chinese ccRCC patients, and immune cell infiltration characteristics are closely correlated with clinicopathological parameters of the patients.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; Immunotherapy ; Male ; Lymphocytes, Tumor-Infiltrating/immunology* ; Female ; Middle Aged ; CD8-Positive T-Lymphocytes/immunology* ; Aged ; T-Lymphocytes/immunology* ; Programmed Cell Death 1 Receptor/immunology* ; Adult ; CD4-Positive T-Lymphocytes/immunology* ; Neoplasm Staging

Ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a vast and diverse family of bioactive peptides. These peptides, synthesized by ribosomes and subsequently modified by various tailoring enzymes, possess a wide chemical space. Among these modifications, radical S-adenosylmethionine (rSAM) enzymes employ unique radical chemistry to introduce a variety of novel peptide structures, which are crucial for their activity. This review examines the major types of modifications in RiPPs catalyzed by rSAM enzymes, incorporating recent advancements in protein structure analysis techniques and computational methods. Additionally, it elucidates the diverse catalytic mechanisms and substrate selectivity of these enzymes through an analysis of the latest crystal structures.
Protein Processing, Post-Translational ; S-Adenosylmethionine/chemistry* ; Ribosomes/metabolism* ; Peptides/metabolism* ; Biological Products/metabolism* ; Humans