“TIL therapy represents a major advancement in personalized cancer treatment, offering new possibilities for patients with treatment-resistant cancers,” said Amod Sarnaik, M.D., lead author and senior member of the Cutaneous Oncology Department at Moffitt.

Tumor-infiltrating lymphocyte therapy has been in development for several decades. Preclinical studies evaluating its efficacy began at the National Cancer Institute (NCI) in the early 1980s. James J. Mulé, IPh.D., a renowned immunologist and associate center director of Translational Science at Moffitt, brought TIL research to the cancer center in 2003. Since then, Moffitt has played a pivotal role in developing and validating the immunotherapy.

In 2010, Moffitt opened its first TIL trials, the first center outside of the NCI to treat patients with the investigational therapy. This initial study, treating 13 patients with advanced metastatic melanoma, yielded promising results: five responses, including two complete responses lasting beyond five years. The commentary examines Moffitt’s subsequent clinical trials, which aimed to address the high dropout rate due to disease progression during TIL manufacturing. These trials combined TIL therapy with newly approved anti-melanoma agents, significantly reducing the dropout rate from 32% to 5%.

Moffitt is also working on the next generation of TIL therapy. Shari Pilon-Thomas, Ph.D., and other immunologists at the center are investigating innovative ways to stimulate and improve TIL therapy growth and manufacturing and determine the best infusion timing to ensure optimal patient outcomes. Moffitt researchers are also expanding this therapeutic approach to treat other solid tumor cancer types, such as lung, sarcoma, cervical and bladder.

“We are at the beginning of unlocking the potential of T-cell and cell therapies for treating advanced cancers. The FDA’s approval of lifileucel is a monumental step to inspire further investment and innovation in T-cell therapies, particularly TIL therapy,” said Moffitt President and CEO Patrick Hwu, M.D. “Our pioneering research at Moffitt into next-generation TIL therapies aims to extend these lifesaving treatments to a broader range of cancer patients.”

Arctic peatlands store vast amounts of carbon. As global temperatures increase and environments change in response, the stability of the carbon stored in these habitats has emerged as a pressing concern. Researchers delved deep into the soil microbiome, scrutinizing the functions of thousands of microorganisms in an Arctic peatland ecosystem. Contrary to previous assumptions, the study revealed that many microorganisms metabolize polyphenols. Scientists had believed that this complex class of carbon compounds was inert and an important part of carbon storage. Armed with this new insight, scientists are better equipped to forecast the impacts of climate change on Arctic ecosystems and devise targeted strategies for mitigating these effects.

Peatlands have long intrigued scientists as reservoirs of terrestrial carbon, yet the role of microorganisms in carbon cycling has remained enigmatic. Contrary to past assumptions, this new research challenges the notion that peatland microorganisms exclusively degrade polyphenols under oxygenated conditions using phenol oxidase. Drawing from insights derived from other oxygen-limited environments like the human gut and rumen, where alternative enzymes and pathways metabolize polyphenols, the research team developed a novel computational tool to rapidly profile polyphenol metabolisms in microbial genomes. This software, applied to thousands of microbial genomes sampled from an Arctic peatland, unveiled a surprising diversity of polyphenol-transforming biochemical pathways. Remarkably, certain microorganisms encoded a profusion of these genes, signifying a polyphenol degradation prowess. Furthermore, the findings highlight the adaptability of microbial gene expression to shifts in soil redox conditions across the landscape.

By uncovering this hidden biochemistry, this research pioneers a new understanding of carbon cycling in these climate critical ecosystems. These insights not only expand knowledge of microbial metabolism but also underscore the intricate interplay between microorganisms and carbon dynamics in the face of climate change.

This material was based on work supported by the Department of Energy (DOE) Office of Science, Biological and Environmental Research Program, as well as the National Sciences Foundation Biological Integration Institute. A portion of this research was performed under the DOE Facilities Integrating Collaborations for User Science program and used resources at the Joint Genome Institute and the Environmental Molecular Sciences Laboratory, both DOE Office of Science user facilities.