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- Title
Serum levels of soluble B and T lymphocyte attenuator predict overall survival in patients undergoing immune checkpoint inhibitor therapy for solid malignancies.
- Authors
Gorgulho, Joao; Roderburg, Christoph; Heymann, Felix; Schulze‐Hagen, Maximilian; Beier, Fabian; Vucur, Mihael; Kather, Jakob N.; Laleh, Narmin Ghaffari; Tacke, Frank; Brümmendorf, Tim H.; Luedde, Tom; Loosen, Sven H.
- Abstract
Therapy with immune checkpoint inhibitors (ICIs) can lead to durable tumor control in patients with various advanced stage malignancies. However, this is not the case for all patients, leading to an ongoing search for biomarkers predicting response and outcome to ICI. The B and T lymphocyte attenuator (BTLA) is an immune checkpoint expressed on immune cells that was shown to modulate therapeutic responses. Here, we evaluate circulating levels of its soluble form, soluble B and T lymphocyte attenuator (sBTLA), as a biomarker for the prediction of treatment response and outcome to ICI therapy. Serum levels of sBTLA were analyzed by multiplex immunoassay in n = 84 patients receiving ICI therapy for solid malignancies and 32 healthy controls. BTLA expression was evaluated on peripheral blood mononuclear cells in a subset of patients (n = 6) using multicolor flow cytometry. Baseline sBTLA serum levels were significantly higher in cancer patients compared to healthy controls. Importantly, circulating sBTLA levels were an independent prognostic factor for overall survival (OS). As such, patients with initial sBTLA levels above the calculated prognostic cutoff value (311.64 pg/mL) had a median OS of only 138 days compared to 526 for patients with sBTLA levels below this value (P =.001). Uni‐ and multivariate Cox regression analyses confirmed the prognostic role of sBTLA in the context of ICI therapy. Finally, we observed a significant correlation between sBTLA levels and the frequency of CD3 + CD8 + BTLA+ T cells in peripheral blood. Thus, our data suggest that circulating sBTLA could represent a noninvasive biomarker to predict outcome to ICI therapy, helping to select eligible therapy candidates. What's new? While immune checkpoint inhibitors (ICIs) boost survival in some cancer patients, response rates and toxicities vary. Anticipating divergent responses and tolerance to ICIs requires the discovery of novel biomarkers and predictive criteria. This study identifies a predictive association between soluble B and T lymphocyte attenuator (sBTLA), an immune regulatory receptor, and overall survival following ICI therapy in a range of tumor entities. Patients with sBTLA levels below an ideal cut‐off value before and during ICI treatment survived significantly longer compared to patients with high sBTLA concentrations. Analyses further show that sBTLA levels correlate with BTLA expression on peripheral cytotoxic lymphocytes.
- Subjects
MONONUCLEAR leukocytes; OVERALL survival; IMMUNE checkpoint inhibitors; T cells; B cells; IPILIMUMAB; HOMOGRAFTS; IMMUNOSUPPRESSION
- Publication
International Journal of Cancer, 2021, Vol 149, Issue 5, p1189
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.33610