{"doi":"10.3389/fimmu.2023.1214843","title":"Editorial: Lymphocyte functional crosstalk and regulation, volume II","abstract":"The immune system consists of specialized cells to perform specific activities to protect the body against various insults including cancer and infections (1). Immune cells often cooperate to mount effective immune responses (2). However, immune responses can be diminished by escape mechanisms employed by ever-evolving tumor cells and pathogens. Escape mechanisms often lead to acquired resistance to therapies (3)(4)(5)(6). Crosstalk among a heterogeneous group of immune cells determines the therapeutic outcomes of immunotherapies.Bulk RNA, single-cell RNA, and targeted next-generation sequencing technologies and computational approaches have greatly improved our understanding of immune subsets and their functional trajectories during disease progression (7,8). Moreover, these technologies are advancing translational research and clinical applications. In this editorial, we highlight the findings of six articles featured in \"Lymphocyte Functional Crosstalk and Regulation: Volume II\". As with Volume I (9), articles in Volume II provide novel insights into the interactions among immune cells in specialized microenvironments and emphasize the importance of considering these unique interactions when developing immunotherapeutic strategies (Fig. 1A-F) (10)(11)(12)(13)(14)(15).Clear cell Renal Cell Carcinoma (ccRCC) is a heterogeneous, aggressive cancer representing ~70% of all RCCs (16,17). It is difficult to predict the outcome of extensively used ICB treatment in ccRCC based on known immune molecular biomarkers (18). Few genomics-based studies have explored immunologic mechanisms at the tumor-immune interface in ccRCC (19). Wu et al. selected an 84-gene panel in ccRCC patients and classified them by using the CNMF algorithm in two distinct ccRCC molecular clusters, C1 (N=176) and C2 (N=333) in TCGA data (10). Investigators discovered how immune escape pathways disrupt the positive effect of immune cell infiltration in 'cluster 1' but not in 'cluster 2'. Their findings emphasize the genomics-based evaluation of immune-tumor crosstalk during patient selection strategies (18). NKT are a unique subset of T-cells that recognize glycolipid antigens. The reciprocal interaction between DC:NK (22) and DC:NKT is of great interest since NKT can produce a diverse range of cytokines (23). Zhao and Yang reviewed reciprocal interactions between NKT and DC to facilitate the adaptive immune response against infections (12). It is known that TCR-expressing NKTcells share features of NK and T-cells (24). Cytokines secreted from NKT can induce DC maturation and facilitate T-cell activation. The review evaluates NKT subsets -NKT1, NKT2, NKT10, and NKT17 -regarding their differential ability to produce cytokines, occurrence in specific tissues, and transcriptional profiles. In addition, the unique characteristics of functional NKT subsets and their lipid ligands that cause NKT activation are discussed. An unproductive cancer antigen processing and presentation remains a dominant mechanism of immune escape (3,(27)(28)(29). Seliger and Massa highlighted how activation of oncogenic pathways and inactivation of tumor suppressor genes produces hypoxic tumor-promoting TME (15). Authors described several detrimental consequences of constitutively activated tumor intrinsic oncogenic pathways (K-RAS mutation, TSG liver kinase B mutation, WNT-b-catenin pathway, myc oncogene amplification, overexpression of HER-2/EGFR genes) on a variety of immune cells. Similarly, the impact of a loss of the tumor-suppressor gene, PTEN, on T-cell infiltration and Treg frequency was discussed (30). The immunological consequences and role of ten-eleven translocation (TET) family mutations in hematologic malignancy, IDH-1/2 mutation in Glioma (31), inactivation of von Hippel Lindau (VHL) in RCC are highlighted (32). Moreover, the immunoregulatory role of tumor growth receptors, the evolution of genomic alteration, secreted cytokines/chemokines in the context of specific cancer, and","journal":"Frontiers in Immunology","year":2023,"id":407414,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336919,"name":"Menaka C. Thounaojam","orcid":"0000-0002-3422-2053","position":1,"is_corresponding":false},{"id":625573,"name":"Francesco M. Marincola","orcid":"0000-0001-6423-391X","position":2,"is_corresponding":false},{"id":250501,"name":"Anil Shanker","orcid":"0000-0001-6372-3669","position":3,"is_corresponding":false},{"id":244690,"name":"Raghvendra M. Srivastava","orcid":"0000-0001-6545-3957","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:21:10.867368Z","pmid":"37266417","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}