Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Superior vena caval obstruction syndrome in small cell lung cancer

In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency. Copyright © 1986 American Cancer SocietySCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Melanoma early detection and awareness: how countries developing melanoma awareness programs could benefit from melanoma-proficient countries

Risk factors for melanoma are well known and have guided plans for primary and secondary prevention. The presentation of the disease, however, varies widely depending on the geographic area, ethnicity, and socioeconomic status. For this reason, many countries have developed specific strategies to increase public awareness and favor early diagnosis. Awareness campaigns, doctor education, and screening of high-risk subjects have all contributed to improve disease outcome in developed countries. The role of primary care physicians is particularly relevant in this regard. Developing countries are trying to implement similar measures. Future efforts to further improve the efficacy of preventive strategies should focus on populations that usually escape campaigns, such as elderly men and people with low socioeconomic status. Fast-growing tumors also require specific attention