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Marais and colleagues report that checkpoint inhibitor treatment of patients with melanoma leads to dynamic changes in peripheral T cells and expansion of immune effector cells. This awakening of the immune system occurs early after treatment and could be exploited in the clinic.
Kupper and colleagues introduce the T-cell fraction as a molecular assessment of T-cell-mediated antitumor responses in primary melanomas that can predict metastatic recurrence.
Cong et al. show that MTSS1 suppresses breast cancer initiation by promoting ubiquitin-mediated suppression of the NF-κB pathway. Loss of this regulatory mechanism promotes the activation and expansion of tumor-initiating cells.
Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.
Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.
Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.
Ryan and colleagues analyze genomic features in tumors from African Americans and European Americans and find that homologous recombination deficiency is more prevalent in African Americans.
Iacobuzio-Donahue and colleagues use integrated transcriptomic, histologic and mutational data to analyze squamous features of pancreatic ductal adenocarcinoma (PDAC), further refining the understanding of heterogeneity and evolution in PDAC.
Ajona and colleagues report that short-term starvation synergizes with anti-PD-1 blockade to reduce lung tumor growth and metastasis. This antitumor effect is mediated through the reduction of plasma IGF-1 levels and IGF-1R levels on tumor cells.
The authors identify a population of L1CAM-positive cells that, following loss of epithelial integrity, promote intestinal tissue regeneration and mediate metastasis initiation and chemoresistance in colorectal cancer.
Ribas and colleagues report that inhibition of PAK4 improves response to anti-PD-1 immunotherapy by reducing Wnt pathway activation and increasing tumor infiltration by T cells.
Martínez-Jiménez et al. report how disruption of the ubiquitin–proteasome system affects cancer, estimating that >10% of driver mutations involve alterations in genes relevant in ubiquitin-mediated proteolysis, including E3 ligases and their targets.
Wu et al. develop trispecific antibodies that recognize CD38, CD3 and CD28 and induce T cell activation and co-signaling. They show in mice and non-human primates that by engaging multiple targets, these antibodies induce enhanced tumor-cell killing.