Exploring the Dynamics of B Cell Subpopulations in Response to Immune Checkpoint Inhibitors: A Prospective Study

Abstract

Globally, the efforts to find the best cancer treatment are demanding and very intensive. Immunotherapy has gained an important role as a second or sometimes first line of treatment for various types of cancer. PD-1/PD-L1 checkpoint inhibitors are an impending category of immunotherapy, and their mechanism, as well as their interaction with T cells, are well studied. However, our knowledge about any possible effect(s) of immunotherapy on B cells is limited. In this prospective study, we asked the question of any possible alterations of circulating B cells (numbers and subsets) occurring during immunotherapy in patients with cancer and of the potential correlation of such changes with the outcomes and with development of immune-related adverse events (irAEs). We enrolled 20 cancer patients who received PD-1 checkpoint inhibitors and 8 healthy donors (HD). Patients underwent regular clinical assessment and imaging using the iRECIST criteria for 6 months following immunotherapy. Peripheral blood samples were collected before and during PD-1 checkpoint inhibitor therapy, and flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) was performed, evaluating various circulating B cell subset phenotypes, including mature naïve B cells, memory B cells, regulatory B cells (Bregs), antibody-secreting cells (ASCs), and age-related B cells (ABCs). Statistical analysis was employed to compare the differences of B cells between different groups and among sequential data within the same group. Total circulating CD19+ B cell counts remained stable across both groups (responders (R), nonresponders (NR)) and timepoints. However, there was a significant rise in mature naïve B cells and decline in memory B cells at the initiation of the treatment in the R group compared to healthy donors and to the NR group. Such changes were correlated with a good response to immunotherapy. On the contrary, higher numbers of ABCs at baseline were seen in the NR group and were correlated with resistance to treatment. As far as immune-related adverse events are concerned, no significant changes were recorded among the different B cell subpopulations evaluated in both groups. Our study provides preliminary data suggesting that B cell subset changes during immunotherapy may correlate with immune checkpoint inhibitor-induced clinical responses in patients with neoplasia. Further investigations to delineate the potential role(s) of B cells in patients undergoing immunotherapy are needed.