Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy.

Oxidative stress, that is, an unbalanced increase in reactive oxygen species (ROS), contributes to tumor-induced immune suppression and limits the efficacy of immunotherapy. Cancer cells have inherently increased ROS production, intracellularly through metabolic perturbations and extracellularly through activation of NADPH oxidases, which promotes cancer progression. Further increased ROS production or impaired antioxidant systems, induced, for example, by chemotherapy or radiotherapy, can preferentially kill cancer cells over healthy cells.

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells.

A new approach to postvasectomy semen analyses eliminates the need to evaluate a fresh specimen.

Background: According to current guidelines, confirmation that vasectomy results in sterility depends on microscopic examination of postvasectomy semen for the presence of spermatozoa. Guidelines established in 2012 require examination of a fresh specimen within 2 h of collection, which necessitates the patient making an appointment with either the surgeon's office or a licensed clinical laboratory. Twenty-five to 42% of patients fail to comply with postvasectomy semen analysis (PVSA).

Trogocytosis and fratricide killing impede MSLN-directed CAR T cell functionality.

Successful translation of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors has proved to be troublesome, mainly due to the complex tumor microenvironment promoting T cell dysfunction and antigen heterogeneity. Mesothelin (MSLN) has emerged as an attractive target for CAR T cell therapy of several solid malignancies, including ovarian cancer. To improve clinical response rates with MSLN-CAR T cells, a better understanding of the mechanisms impacting CAR T cell functionality is crucial.

Targeting of Nrf2 improves antitumoral responses by human NK cells, TIL and CAR T cells during oxidative stress.

Background: Adoptive cell therapy using cytotoxic lymphocytes is an efficient immunotherapy against solid and hematological cancers. However, elevated levels of reactive oxygen species (ROS) in the hostile tumor microenvironment can impair NK cell and T cell function. Auranofin, a gold (I)-containing phosphine compound, is a strong activator of the transcription factor Nrf2.