Eating away T cell responses in lung cancer

Abstract

Despite evidence for clinical benefit in patients suffering from lung cancer following treatment with immune checkpoint inhibitors (ICI), it is still uncertain how to predict which patients are likely to experience a significant response. In their work, Valencia et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220726) identify the DSTYK kinase as a cancer cell–intrinsic modulator of response to immunotherapy. Through regulation of the mTOR pathway and stimulation of protective autophagy, DSTYK blunts CD8+ T cell–mediated killing of cancer cells. Accordingly, lung cancers with increased expression of DSTYK are less responsive to ICI treatment. These observations could be useful in the clinic towards the development of predictive biomarkers and novel therapeutic strategies.

Imaging glucose metabolism to reveal tumor progression

“…The transition to aerobic glycolysis is a characteristic of advanced cancers and is easily assessed by 18F-FDG-PET ( Zhao et al, 2022 ). A crucial route governing the development and metabolism of these malignancies is the mechanistic target of the rapamycin (mTOR) pathway, which can be efficiently addressed by utilizing selective catalytic mTOR kinase inhibitors ( Ferrara and Roz, 2022 ). This was investigated in mice with lung cancer, where therapeutic response was evaluated using 18F-FDG-PET and computed tomography (CT) imaging before and after the administration of mTOR inhibitor MLN0128 ( Momcilovic et al, 2018a ; Momcilovic et al, 2018b ).…”