Abstract
Identification of reliable biomarkers to predict efficacy of immune checkpoint inhibitors and to monitor relapse in cancer patients receiving this therapy remains one of the main objectives of cancer immunotherapy research. We found that the pretreatment B cell number in the peripheral blood differed significantly between responders and non-responders to anti-PD-1-based immunotherapy. Patients with various cancer types achieving a clinical response had a significantly lower number of B cells compared with those with progressive disease. Patients who progressed from partial response to progressive disease exhibited a gradually increased number of circulating B cells. Our findings suggest that B cells represent a promising biomarker for anti-PD-1-based immunotherapy responses and inhibit the effect of PD-1 blockade immunotherapy. Thus, preemptive strategies targeting B cells may increase the efficacy of PD-1 blockade immunotherapy in patients with solid tumors.
Highlights
Therapeutic blocking of the programmed death-1 (PD-1) pathway has recently been shown to be a promising strategy for treating solid tumors, rendering long-term survival possible [1]
We set out to identify a reliable biomarker that can be used to predict the response to antiPD-1-based immunotherapy, and our results strongly suggest that pretreatment levels of B cells are highly predictive of immunotherapy response
Similar results were observed when absolute numbers of lymphocyte subsets were analyzed (Figures 1B,D), except that the value of natural killer (NK) cells was higher in partial response (PR) patients (Figure 1F). These results indicated that the frequency of B cells in the peripheral blood is associated with efficacy of immunotherapy and might be a potential biomarker for predicting response in patients who receive anti-progressive disease (PD)-1based therapy
Summary
Therapeutic blocking of the programmed death-1 (PD-1) pathway has recently been shown to be a promising strategy for treating solid tumors, rendering long-term survival possible [1]. Only a minority of patients benefit from this treatment. Identification of reliable predictors of response to PD-1 blockade is of utmost importance for determining the most appropriate therapy candidates. PD-L1 overexpression is the most logical biomarker to predict patient response to anti-PD-1 therapy; various shortcomings limit its clinical utility, including variability in detection antibodies and differing immunohistochemistry cutoffs [2]. Other reports suggest that potential biomarkers could include tumor-infiltrating lymphocytes, mutational burden, and immune gene signatures [3]. The main obstacle for these biomarkers is the need to obtain tumor biopsies, which is often not feasible, especially for patients with poor performance status or who need to begin therapy urgently. Even the use of these tumor-based factors fails to reliably identify potentially responsive patients
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