Abstract 5403: Meeting the Physical Activity Guidelines is associated with increased CD8+ T-cell density in the tumor microenvironment of breast cancer patients
Authors: Cannioto Rikki , Omilian Angela , Davis Evan , Mendicino Lucas , Abrams Scott , Qin Bo , Hong Chi-Chen , Bandera Elisa , Yao Song , Ambrosone Christine 
Published: March 2024

Abstract
Background: Our current understanding of how physical activity (PA) is associated with immunity in breast cancer (BC) patients is based on pre-clinical evidence gleaned from mouse models or immune cells in the circulating blood, which may not be reflective of the tumor immune microenvironment (TIME). Whether self-reported PA is associated with immune cell infiltration in the breast TIME, the most relevant site for prognosis, remains a fundamental gap in knowledge. Herein, we examined the association of self-reported PA in the year before BC diagnosis with CD8+ T-cell density in the breast TIME. As prior evidence from healthy adults suggests the relationship between exercise and immunity is not linear, we hypothesized that patients reporting the highest PA level would not have the highest CD8+ T-cell density in their tumor.
Methods: We leveraged data and tumor samples from 685 women with BC (548 self-identified Black and 137 self-identified White) enrolled in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study. CD8+ T-cell density per square millimeter of tumor tissue was derived from IHC staining of tissue microarrays. Weekly PA in the year before diagnosis was categorized as inactive; low active (&lt;7.5 MET hours/week); moderately active [7.5-14.9 MET hours/week, the equivalent of meeting the minimum PA Guidelines (PAG)]; or high active (≥15.0 MET-hours/week, exceeding the minimum PAG). Log transformed mean CD8+ T-cell densities were compared by PA level using t-tests and multivariable linear regression with adjustment for age, race, estrogen receptor status, and tumor grade.
Results: Meeting the minimum PA Guidelines was associated with significantly higher CD8+ T-cell density in the breast TIME [120.4 (353.6)] in comparison to inactivity [62.0 (154.5), p=0.02]. Although there were also distinct differences in T-cell density between moderate and low-active patients [120.4 (353.6) versus 69.5 (172.6), p=0.10] and moderate and high-active patients [120.4 (353.6) versus 80.7 (223.3), p=0.051], associations were shy of significance. Multivariable linear regression analyses confirmed that moderately active patients had significantly higher CD8+ T-cell density in comparison to inactive patients, overall (p=0.029), and among Black patients (p=0.021).
Conclusions: In comparison to inactivity, BC patients meeting the PAG (moderate activity) had significantly increased CD8+ T-cell density in their tumor, which is associated with better survival outcomes. This new translational knowledge suggests exercise-induced immunomodulation may be an important molecular mechanism underlying the association of PA with improved BC survival. As the immune system is a key player in treatment response and efficacy, further study of the role that PA ancillary to therapy may play in improving treatment and survival outcomes is warranted.
Citation Format: Rikki Cannioto, Angela Omilian, Evan Davis, Lucas Mendicino, Scott Abrams, Bo Qin, Chi-Chen Hong, Elisa Bandera, Song Yao, Christine Ambrosone. Meeting the Physical Activity Guidelines is associated with increased CD8+ T-cell density in the tumor microenvironment of breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5403.