The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role of intratumoral T-cells and their association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated with PD-1 axis blockers. QIF is used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load, candidate class-I neoantigens or intratumoral CD3 signal are significantly associated with favorable response to therapy. Additionally, a “dormant” TIL signature is associated with survival benefit in patients treated with immune checkpoint blockers characterized by elevated TILs with low activation and proliferation. We further demonstrate that dormant TILs can be reinvigorated upon PD-1 blockade in a patient-derived xenograft model.
Abstract-It is well-known that malware constantly evolves so as to evade detection and this causes the entire malware population to be non-stationary. Contrary to this fact, prior works on machine learning based Android malware detection have assumed that the distribution of the observed malware characteristics (i.e., features) do not change over time. In this work, we address the problem of malware population drift and propose a novel online machine learning based framework, named DroidOL to handle it and effectively detect malware. In order to perform accurate detection, the security-sensitive behaviors are captured from apps in the form of inter-procedural control-flow sub-graph features using a state-of-the-art graph kernel. In order to perform scalable detection and to adapt to the drift and evolution in malware population, an online passiveaggressive classifier is used.In a large-scale comparative analysis with more than 87,000 apps, DroidOL achieves 84.29% accuracy outperforming two state-of-the-art malware techniques by more than 20% in their typical batch learning setting and more than 3% when they are continuously re-trained. Our experimental findings strongly indicate that online learning based approaches are highly suitable for real-world malware detection.
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