Numerous studies have shown that the composition of the fecal microbiota is a factor impacting the response to immunotherapy-type anticancer drugs. This is particularly true during dysbiosis induced after taking antibiotics. This finding opened the door to the possibility of using gut microbiota-centered interventions to improve the likelihood of patient response to immunotherapies. One of the gut microbiota-centered therapy is fecal microbiota transplantation (FMT), already used in the treatment of certain intestinal pathologies. Understanding how FMT impacts intestinal and anti-tumor immunity is the challenge of tomorrow to improve the care of patients living with cancer. The use of the Olink Cytokine Panel in our FMT models makes it possible to highlight a variation in the immune tone of the transplant recipient.

To facilitate translational research on diabetic kidney disease, we developed the Joslin Kidney Panel (JKP), a panel of 21 circulating proteins strongly associated with risk of kidney function decline and progression to ESKD. Using a custom-made OLINK multiplex platform of assays with excellent specificity, precision, and accuracy, we quantified 21 JKP proteins in four independent study groups. In the Type 1 diabetes individuals from Joslin (n=59), FinnDiane (n=389) and Steno (n=283), JKP proteins predicted progression to ESKD during 10-year follow-up. Many of these proteins had prognostic performance equal to or better than clinical markers. An optimal model to predict risk of ESKD, which included clinical markers and 8 JKP proteins, was developed for the FinnDiane cohort and validated in the Steno cohort, and had better discrimination than the clinical model alone. By measuring baseline serum concentrations of the JKP proteins in a subgroup of 500 Type 2 diabetes individuals from the ACCORD trial, we identified 3 proteins that predicted amelioration of fast kidney function decline during 6 years of follow-up in those receiving treatment with fenofibrate. In conclusion, 21 JKP proteins measured on the Joslin OLINK platform provided a precision medicine-based approach to identify those at risk of ESKD and those responding to specific reno-protective therapy.

As people age, their immune function gradually declines, coinciding with increased cancer rates. However, the precise reasons behind age-related dysfunction of CD8+ T cells in cancer remain unclear. Our study reveals that tumor growth accelerates in older tumor-bearing mice due to diminished infiltration and function of CD8+ T cells. Even when young, tumor antigen-specific CD8+ T cells are transferred into aged hosts, they fail to combat tumors effectively. This failure is related to the rapid onset of CD8+ T cell dysfunction triggered by cell-extrinsic signals from the aged tumor microenvironment. Given that aging is typified by a persistent, low-level inflammation termed inflammaging across various tissues, we wonder whether a specific type of pro-inflammatory cytokine or chemokine is the potential cell-extrinsic signal in the aged tumors that causes CD8+ T cell dysfunction. We then utilize the Olink Target 48 Mouse Cytokine platform to explore the interplay of cytokines and chemokines within both the aging hosts generally and the aged tumors locally. In summary, our research delves into the cell-extrinsic signals (e.g., pro-inflammatory cytokine or chemokine) influencing CD8+ T cell response in aged tumors and proposes potential therapeutic approaches to enhance CD8+ T cell control of cancer.  Learning Objectives  •Understand the potential mechanism of how the aged tumor microenvironment limits CD8+ T cell control of cancer. •Discover proper therapeutic approaches to reinvigorate CD8+ T cell effector function in aged tumors. •