Mechanisms of acquired resistance to immune checkpoint inhibitors (ICIs) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell surface HLA class I expression in the tumor and a matched patient-derived xenograft (PDX). Downregulation of B2M was also found in two additional PDXs established from ICI-resistant tumors. CRISPR-mediated knock-out of B2m in an immunocompetent lung cancer mouse model conferred resistance to PD-1 blockade in vivo proving its role in resistance to ICIs. These results indicate that HLA Class I APM disruption can mediate escape from ICIs in lung cancer.

Designing adequate control laws for grid-connected inverters with LCL filters is complicated. The power quality standards and the system resonances burden the task. In order to deal with resonances, system damping has to be implemented. Active damping is preferred to passive damping so as to improve the efficiency of the conversion. In addition, paralleled grid-connected inverters in photovoltaic (PV) plants are coupled due to grid impedance. Generally, this coupling is not taken into account when designing the control laws. In consequence, depending on the number of paralleled grid-connected inverters and the grid impedance, the inverters installed in PV plants do not behave as expected. In this paper, the inverters of a PV plant are modeled as a multivariable system. The analysis carried out enables to obtain an equivalent inverter that describes the totality of inverters of a PV plant. The study is validated through simulation and field experiments. The coupling effect is described and the control law design of paralleled grid-connected inverters with LCL filters in PV plants is clarified.