Data from <i>Escherichia coli</i>–Specific CXCL13-Producing T<sub>FH</sub> Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer

<div>Abstract<p>Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4<sup>+</sup> T cells (T<sub>FH</sub>) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. T<sub>FH</sub> were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory T<sub>FH</sub> accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4<sup>+</sup>CD38<sup>+</sup> T<sub>FH</sub> residing in bladder tissues correlated with clinical benefit. Finally, T<sub>FH</sub> and IgG directed against urothelium-invasive <i>Escherichia coli</i> dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale.</p>Significance:<p>In patients with bladder cancer treated with neoadjuvant pembrolizumab, <i>E. coli</i>–specific CXCL13 producing T<sub>FH</sub> and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against <i>E. coli</i> might be harnessed for future therapeutic strategies.</p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-12-10-ITI" target="_blank">This article is highlighted in the In This Issue feature, p. 2221</a></i></p></div>