T peripheral helper (Tph) cells, a marker of immune activation in cancer and autoimmune disorders

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-09, Vol.266, p.110325, Article 110325
• Main Authors: del Carmen Crespo Oliva, Celia, Labrie, Marilyne, Allard-Chamard, Hugues
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Autoimmune Diseases - immunology; B-Lymphocytes - immunology; cancer; Humans; Inflammation; Neoplasms - immunology; T peripheral helper cells; T-Lymphocytes, Helper-Inducer - immunology; Tertiary lymphoid structures
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110325

T peripheral helper (Tph) cells are a newly discovered subtype of CD4+ T cells that have emerged as the counterpart of T follicular helper (Tfh) cells in the peripheral tissues. These two cell types share some common characteristics, such as high levels of PD1 and CXCL13 expression, but differ in the expression of transcription factors and chemokine receptors. Tph cells have been studied in relation to B cells' effector functions, including cytokines production and antibody-mediated immune responses. However, their role in the inflammatory-mediated development of malignancies remains poorly understood. Tph cells were initially identified in the synovium of rheumatoid arthritis patients and have since been found to be expanded in several autoimmune diseases. They have been linked to a worse prognosis in autoimmune conditions, but intriguingly, their presence has been correlated with better outcomes in certain types of cancer. The functions of Tph cells are still being investigated, but recent data suggests their involvement in the assembly of tertiary lymphoid structures (TLS). Furthermore, their interaction with B cells, which have been mainly described as possessing a memory phenotype, promotes their development. In this review, we explore the role of Tph cells in peripheral immune responses during cancer and autoimmune disorders. •Tph cells have been implicated in the induction of ectopic lymphoid structures.•Increasing data suggest a transition from Tfh into Tph cells.•Upon antigen stimulation, Tph cell activation is regulated by concomitant PD-1 signaling.•Pathways controlled by Tph activation have been characterized in the early stages of ADs as a leading contributor to the perpetuation of chronic inflammation. Hence it would be rational to address Tph cells as putative targets in preventing ADs establishment in its early stages.•Triggering TLS neogenesis and promoting humoral responses is a pivotal antitumoral function of Tph cells; however, recent studies on breast cancer suggest an alternative antitumoral role of Tph based on limiting Treg expansion.