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NIH grant 1R01CA316160-01: Role of Allostatic Load in Immunotherapy Outcomes
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: LINDSAY G. COWELL. Award: $389844.
Start: 2026-09-24T00:00:00.
Project Summary/Abstract
Disparities in cancer outcomes reflect a multifaceted interaction between multiple characteristics of patients.
Allostatic load (AL) – a composite of neuroendocrine, immune, metabolic, and cardiovascular parameters –
represents accumulated, chronic stress responses. AL provides additional insight beyond individual socio-
demographic and economic risk factors by capturing the synergy of multilayered and interactive variables that
promote health gaps. Higher in vulnerable populations (including those of multiethnic and lower income
communities), this metric has been associated with increased risk of cancer, other chronic diseases, and
mortality. Notably, AL has not been studied in the context of cancer immunotherapy outcomes. Furthermore,
immunotherapy clinical trials have enrolled patients across all populations, and the few studies examining
multiethnic patients have suggested the possibility of inferior outcomes. Unlike any other anti-cancer therapy,
immunotherapy relies on patient organ systems and physiology for clinical effects. Therefore, aspects of host
immune function are likely central determinants of treatment efficacy and toxicity. However, research into clinical
biomarkers for the selection and tracking of immunotherapy regimens has focused almost exclusively on tumor
characteristics as opposed to patient characteristics and immune function. To address this critical gap in current
knowledge, we have assembled an institutional immuno-oncology registry (N>700) featuring diverse patient
populations, detailed clinical data, serial biospecimen collection, and various immunoregulatory assays. Through
progressive stages of AL, shifts in stress hormones, inflammatory cytokine/chemokine profiles, immune cell
subset composition and recirculation, downstream signaling intermediates, and variability in single-cell RNA
sequences may correlate with immune status. We therefore hypothesize that elevated AL is associated with
worse immunotherapy outcomes and underlying biological and immunological mechanisms. This will be
evaluated through the following Specific Aims: (1) Determine the association between AL, patient
characteristics, and immunotherapy outcomes, (2) Identify the correlation between AL and immune function by
quantifying soluble mediators of stress and inflammation, and (3) Characterize the correlation between AL and
immune cell status using a single-cell multiomics approach – single-cell RNA sequencing (scRNA-seq) and cell
surface receptor protein profiling. We will leverage baseline, pre-treatment blood samples (of >700
immunotherapy registry patients), patient characteristics (demographic and socioeconomic), electronic health
record data for clinical characteristics, stored biospecimens, and perform new assays to calculate the AL score
for each registry patient. In summary, AL, a complex, multifactorial composite index of stress and social
determinants, may provide biological and immunological insights into health gaps to develop improved
personalized immunotherapeutic regimens for better immuno-oncology outcomes in patients across diverse
populations.document fetched 2026-10-04 02:44