ANK Therapeutic Prospects and Usefulness of PD-L1 and NK Activity as Biomarkers for Predicting Treatment Efficacy Revealed from the Treatment Course of Patients with HTLV-1-Associated Bronchioloalveolar Disease

Cancer Med J. 2023;6(1):30-36. Epub 2022 Sep 13.

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with poor prognosis that can present as HTLV-1-associated bronchioloalveolar disease (HABA). Chemotherapy is recommended for ATL; however, it is not very effective against all types of ATL. Furthermore, there are no effective treatments for smoldering HABA-associated ATL. We present a case in which amplified natural killer cell (ANK) therapy was effective in a woman in her early 80s who was previously diagnosed with ATL-related smoldering HABA and presented with dyspnea and productive cough on exertion. The symptoms were suppressed for approximately 10 months after the first treatment, but then gradually worsened. About a year later, a second treatment was followed by mild side effects. Suppression of ATL cell proliferation by repeated doses of ANK therapy appears to be effective in this patient. The therapeutic effect was high even with long treatment intervals, and the efficacy and safety of repeated treatments have been demonstrated. ANK therapy is expected to be the mainstay of treatment ATL and HABA. ANK therapy has been reported to kill PD-L1 positive tumor cells and some solid tumors with excellent responses have many PD-L1-positive tumor cells. ANK therapy is thought to be effective for ATL because there are many PD-L1-positive tumor cells. Furthermore, administration of activated NK cells may increase tumor-killing activity in those patients with reduced NK activity. While future studies are needed, PD-L1 positive rate and NK activity may be biomarkers for the effectiveness of ANK therapy.

Keywords: ANK therapy; Activated NK; Adult T-cell leukemia; Diffuse panbroncheolitis; HTLV-1-related bronchiolo-alveolar disorder; PD-L1.