Weekly Digests

2021

August

Checkpoint inhibition clears the way for subsequent MAPK inhibition

August 25, 2021

Even though MAPK inhibitors (MAPKi, such as BRAFi or MEKi) can be an effective treatment strategy, therapy resistance limits their benefits. However, in clinical studies, patients with BRAFV600E/K metastatic melanoma, who had received prior treatment with checkpoint inhibitors, had increased efficacy of MAPKi with longer progression-free survival. Therefore, Wang, Liu, Yang, and Algazi...

Epigenetic scarring leaves T cells permanently exhausted

August 18, 2021

T cell exhaustion is accompanied by a distinct and relatively well described epigenetic state, but whether that state is reversible is not quite clear. Investigating this, Yates et al. explored the chromatin landscape of CD8+ T cells in the setting of active and cured chronic infection, and published the results in Nature Immunology...

It’s not all just PD-1: the CD155/TIGIT axis is essential for immune evasion in pancreatic cancer

August 11, 2021

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is largely refractory to current clinical immunotherapies. Freed-Pastor et al. investigated the immune evasion mechanisms in this cancer type by assessing neoantigen load, neoantigen-specific T cells, and T cell characteristics, revealing a novel axis of inhibition. Their results were recently published in Cancer Cell...

Antigen specificity and phenotype of TILs

August 4, 2021

Tumor-infiltrating lymphocytes (TILs) can exhibit a variety of functional and transcriptional states, but the connection between phenotype and antigen specificity remains unclear, and decoding this relationship could provide insight into patient response to immune checkpoint blockade (ICB) therapy. With this goal in mind, Oliveira et al. and Caushi & Zhang et al. examined...

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