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CXCL13+ T cells appear decisive for response to immune checkpoint blockers; paclitaxel seems to impair their expansion caused by atezolizumab, thus compromising combination therapy effectiveness
In triple-negative breast cancer the benefit of combining chemotherapy with immune checkpoint inhibitors such as anti-PD-L1 is still not very clear. For this reason a group of Chinese researchers examined the role and dynamics of different immune cells in 22 patients with advanced triple-negative breast cancer treated with paclitaxel only or its combination with the anti-PD-L1 atezolizumab. The results, published in Cancer Cell, show that a specific cell subtype, CXCL13+ T lymphocytes, appears to play a key role and must be present in the tumor microenvironment for a clinical response to immunotherapy with immune checkpoint blockers.
The fundamental mechanisms underlying immune checkpoint blockade resistance remain poorly understood but immune cells in tumor microenvironment seem crucial: for this reason, researchers investigated their quality and quantity using analysis such as single-cell RNA-sequencing and ATAC sequencing, with the aim of understanding immune dynamics in patients with advanced triple-negative breast cancer receiving chemotherapy alone or in combination with an anti-PD-L1. The presence of CXCL13+ T cells is predictive of a good clinical response to immunotherapy: high levels of baseline CXCL13+ T cells are linked to the proinflammatory features of macrophages and can predict effective responses to the combination therapy; moreover in responsive patients other immune cells concertedly increase following the combination therapy (such as lymphoid tissue inducer cells or follicular B cells). All these cells decrease after paclitaxel monotherapy, that could therefore compromise atezolizumab effect in these patients. Immune cells dynamics in the tumor microenvironment seem therefore decisive. «Our data highlight the importance of CXCL13+ T cells in effective responses to anti-PD-L1 therapies and suggest that their reduction by paclitaxel regimen may compromise the clinical outcomes of accompanying atezolizumab for triple-negative breast cancer treatment», authors say. «The compendium of our trascriptomic and epigenetic data, coupled with T cell receptor sequences, will provide a rich resource for understanding the functional states and dynamics of immune cells following different treatment regimens in advanced triple-negative breast cancer. An interactive portal has been developed to facilitate the usage of our data for the wide research community».