Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV± cancer.

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV+ head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus. Here, we evaluate multiple aspects of the memory-like natural killer cell response in human-derived bioengineered environments, including immune cell extravasation, tumor penetration, tumor killing, T cell dependence, virus suppression, and compatibility with retroviral medication. Overall, these results suggest that memory-like natural killer cells are capable of operating without T cell assistance and could simultaneously destroy head and neck cancer cells as well as reduce viral latency.

Do immune inflammatory markers correlate with anal dysplasia and anal cancer risk in patients living with HIV?

PURPOSE: People living with HIV (PLWH) are at an elevated risk for developing anal cancer. As screening is invasive, markers predicting those at highest risk for anal cancer could guide individualized screening. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are surrogate inflammatory/immune markers known to correlate with cancer outcomes. This study aims to assess whether these markers correlate with anal cancer risk in PLWH. METHODS: This is a retrospective single-institution cohort study of PLWH at a single academic medical center who were diagnosed with or screened for anal dysplasia between 2001 and 2019. Aforementioned markers collected within one year of diagnosis were recorded. Regression modeling was used to estimate odds of anal cancer. Receiver operating characteristic analysis was utilized to determine optimal cutoff for screening values. RESULTS: Five-hundred-fourteen patients were included. NLR and PNI were significantly associated with cancer risk on univariate (p = 0.03, p = 0.001) and multivariate analyses (p = 0.03, p = 0.01). NLR increased across all grades of dysplasia. PLR was not associated with cancer risk. A NLR of ≥ 1.64 can be utilized to capture 76% of cancer patients in our cohort. CONCLUSIONS: NLR values in patients living with HIV correlate with risk of anal cancer and increasing grades of dysplasia. A cutoff NLR of ≥ 1.64 can be used to help capture those at risk. NLR is a promising marker of risk of anal cancer and progression of anal dysplasia in patients with HIV infection and could be used to risk-stratify screening and surveillance intervals.