IRE1/XBP1 is a sensor of the endoplasmic reticulum stress triggered by excessive protein production demand. This signaling could be dysregulated in immune cells during aberrant processes such as cancer or inflammation. The inhibition of IRE1/XBP1 has been shown to enhance the antitumor effects of paclitaxel, a chemotherapeutic that results in chemotherapy-induced peripheral neuropathy (CIPN). Dr. Romero-Sandoval will indicate that upon in vitro paclitaxel exposure, immune cells acquire a pro-inflammatory phenotype that is recapitulated in a mouse model and cancer patients receiving paclitaxel. The blockade of IRE1/XBP1 by genetic or pharmacological approaches results in a reversal of this inflammatory phenotype and pain-related behaviors in mice. Interestingly, the activation of IRE1/XBP1 in immune cells from cancer patients treated with paclitaxel correlates with the appearance of CIPN symptoms and the severity of the disease. All these data suggest that IRE1/XBP1 is a potential target and biomarker for CIPN.