Induction of immunogenic cell death (ICD) in cancer has been proposed as a promising strategy to elicit potent adaptive immune responses against tumor-associated antigens, potentially overcoming the limited efficacy of immunotherapy in some patients and tumor types. Since type I interferon (IFN) is a key modulator of ICD in antitumor responses, researchers at the University of California, San Diego are investigating how to expand the IFN effect to promote ICD responses in cancer cells.

Upregulation of C-X-C motif chemokine ligand 1 (CXCL1) has been validated in patients with colorectal cancer (CRC), but the mechanism behind CXCL1 affecting CRC tumor cell progression is not clear. Gene-editing techniques were used to investigate the impact of CXCL1 knockout and overexpression in CRC cells.

TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine kinase with an established role coordinating innate immune responses, and it has been previously identified as a candidate immune evasion gene. Additionally, disrupting TBK1 signaling has shown potential for enhancing response to immunotherapy with immune checkpoint blockade (ICB) in murine tumor models.

During metastasis, the mechanical properties of the nucleus make translocation of this organelle the rate-limiting step during constrained migration, and these properties are regulated through interactions between the cytoskeleton, integral nuclear envelope (NE) proteins, the nuclear lamina and chromatin.

Major histocompatibility complex class I (MHC-I) gene promoters are bivalently modified during development, which can be exploited in cancer cells to silence MHC-I expression and evade CD8+ T cells; in cells that exhibit bivalent modification of MHC-I genes, lower levels of cell surface MHC-I can be induced either by PRC2 inhibition or exposing the cells to interferon γ (IFNγ) in conjunction with polycomb inhibition to allow a permissive chromatin status.

Mortality rates related to non-small-cell lung cancer (NSCLC) remain still high, with about 75% of patients getting little clinical benefit from therapy. Adverse conditions in the tumor microenvironment, such as hypoxia or oxidative stress, disrupt the protein-folding capacity of the endoplasmic reticulum (ER) in infiltrating cells, provoking cellular stress that activates the unfolded protein response (UPR) pathway to restore proteostasis in this cellular organelle. During ER stress, serine/threonine-protein kinase/endoribonuclease IRE1 exerts its endoribonuclease activity on XBP1 mRNA generating a splice variant that encodes XBP1s that induces UPR target gene expression.

Researchers from Yale University and affiliated organizations published data from a study that aimed to assess the mechanistic and pathophysiological importance of plaque-associated axonal spheroids (PAASs) in Alzheimer’s disease (AD).

Previous evidence suggests that MEK/BRAF inhibitors targeting aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway can sensitize tumors to immunotherapy through different mechanisms. This occurs in NRAS/BRAF mutant melanoma, where kinase inhibitor treatment sensitizes tumors to immunotherapy, at least partly, through an increase in the average surface presentation of peptide major histocompatibility molecules (pMHC) molecules. However, the optimal combination, order and timing of administration of both therapeutic strategies remain unclear.

Tumors have a lower interstitial pH compared to healthy tissues, with tumor acidity having emerged as a driver of tumor progression as it can lead to tumor immune evasion. Solute carrier family 4 member 4 (SLC4A4), which encodes a sodium bicarbonate cotransporter involved in pH regulation and homeostasis in normal tissue, was the focus of studies in pancreatic cancer resistance in in vivo preclinical models. Researchers tested the impact of Slc4a4 deletion in cancer cells on tumor growth, anticancer immunity and response to immunotherapy in murine models of pancreatic ductal adenocarcinoma (PDAC).