Piloting HealthScore: Feasibility and acceptability of a clinically integrated health coaching program for people living with cancer.

BACKGROUND: Cancer supportive care interventions often have limited generalizability, goal misalignment, and high costs. We developed and piloted a health coaching intervention, UNC HealthScore, in patients undergoing cancer treatment (ClinicalTrials.gov identifier NCT04923997). We present feasibility, acceptability, and preliminary outcome data. METHODS: HealthScore is a six-month, theory-based, multicomponent intervention delivered through participant-driven coaching sessions. For the pilot study, participants were provided a Fitbit, responded to weekly symptom and physical function digital surveys, and met with a health coach weekly to develop and monitor goals. Coaching notes were discussed in weekly interdisciplinary team meetings and provided back to the treating oncology team. Symptom alerts were monitored and triaged through a study resource nurse to relevant supportive care services. Feasibility was determined based on intervention enrollment and completion. Acceptability was based on satisfaction with coaching and Fitbit-wearing and was informed by semistructured exit interviews. Outcomes evaluated for signs of improvement included several PROMIS (Patient-Reported Outcomes Measurement Information System) measures, including the primary intervention target, physical function. RESULTS: From May 2020 to March 2022, 50 participants completed the single-arm pilot. Feasibility was high: 66% enrolled and 71% completed the full intervention. Participants reported an average of 4.8 and 4.7 (out of 5) on the acceptability of coaching calls and using the Fitbit, respectively. Physical function scores rose 3.1 points (SE = 1.1) from baseline to 3 months, and 4.3 (SE = 1.0) from baseline to 6 months, above established minimal clinically important difference (MCID). Improvements above MCID were also evident in anxiety and depression, and smaller improvements were demonstrated for emotional support, social isolation, cognitive function, symptom burden, and self-efficacy. DISCUSSION: HealthScore shows feasibility, acceptability, and promising preliminary outcomes. Randomized studies are underway to determine the efficacy of preserving physical function in patients with advanced cancer.

Tumor suppressor TET2 promotes cancer immunity and immunotherapy efficacy.

Loss-of-function mutations in genes encoding TET DNA dioxygenase occur frequently in hematopoietic malignancy, but rarely in solid tumors which instead commonly have reduced activity. The impact of decreased TET activity in solid tumors is not known. Here we show that TET2 mediates interferon γ (IFNγ)-JAK-STAT signaling pathway to control chemokine and PD-L1 expression, lymphocyte infiltration and cancer immunity. IFNγ stimulated STAT1 to bind TET2 and recruit TET2 to hydroxymethylate chemokine and PD-L1 genes. Reduced TET activity was associated with decreased TH1-type chemokines and tumor-infiltrating lymphocytes (TILs) and the progression of human colon cancer. Deletion of Tet2 in murine melanoma and colon tumor cells reduced chemokine expression and TILs, enabling tumors to evade anti-tumor immunity and to resist anti-PD-L1 therapy. Conversely, stimulating TET activity by systematic injection of its co-factor, ascorbate/vitamin C, increased chemokine and TILs, leading to enhanced anti-tumor immunity and anti-PD-L1 efficacy and extended lifespan of tumor-bearing mice. These results suggest an IFNγ-JAK-STAT-TET signaling pathway that mediates tumor response to anti-PD-L1/PD-1 therapy and is frequently disrupted in solid tumors. Our findings also suggest TET activity as a biomarker for predicting the efficacy and patient response to anti-PD-1/PD-L1 therapy, and stimulating TET activity as an adjuvant immunotherapy of solid tumors.