Tertiary lymphoid structures induced by CXCL13-producing CD4+ T cells increase tumor infiltrating CD8+ T cells and B cells in ovarian cancer

Ukita et al. (BioRxiv) doi: 10.1101/2021.12.01.470493

Keywords

  • Tertiary lymphoid structures

  • Ovarian cancer

  • Tumor infiltrating T cells

  • CD4+ T peripheral helper cells (Tph)

 

Main Findings

In this preprint the authors showed that the tumor infiltrations of CD8+ T and B cells in a cohort of ovarian cancer patients were associated with prolonged survival and with the formation of tertiary lymphoid structures (TLS). They found that TLS in tumor tissues from ovarian cancer patients colocalized with the expression of CXCL13, a chemokine already known to play an important role in TLS formation and largely associated with favourable clinical outcome in different cancer types. Furthermore, RNA in situ hybridization revealed that CD4+ T cells were the critical source of CXCL13 in the early stage of TLS development, while FDCs were shown to be responsible for the maintenance of the mature TLS. TGF-b contributed to the differentiation of CXCL13-producing CD4+ T cells, which adopted a T peripheral helper (Tph) phenotype by expressing PD-1 and lacking CXCR5. The effect of CXCL13 on TLS formation was also confirmed by the authors in an ovarian cancer mouse model. 

Overall this study identifies and suggests CXCL13 as possible candidate to better determining ovarian cancer prognosis and targeting effective antitumor response. 

Limitations

  • Weak TCR repertoire analysis 

  • Lack of functional characterization of Tph cells

  • Lack of functional interaction between humoral and cellular components 

Significance

  • Importance in the cancer field to identify possible factors, and therefore future targets, associated with better prognosis and effective antitumor response

  • Access to human ovarian cancer cohort

Novelty

  • Association between humoral and cellular immunity in antitumor immune response

  • Identification of CXCL13 as a candidate prognostic factor in ovarian cancer

  • Identification of CD4+ Tph cells involvement in TLS in ovarian cancer

 

Credit

Reviewed by Elena Brenna as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford and Karolinska Institute. Follow her on Twitter