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Sarcoma

Sarcoma Poster Presentations 1

P61: Higher body-mass index is associated with decreased circulating and intratumoral natural killer cells in soft tissue sarcoma

Friday, March 22, 2024
10:49am – 10:55am ET
Location: C110
Introduction:

We have previously observed improved survival in soft tissue sarcoma (STS) patients who harbor greater numbers of intratumoral natural killer (NK) cells. However, the impact of immune-modifying variables such as obesity on immune infiltrates in STS is not well-defined. Here, we sought to investigate the relationship between BMI and NK cell populations in the blood and tumor of STS patients.


Methods:

On an IRB-approved protocol, blood and tumor specimens were prospectively collected on 31 STS patients undergoing surgery from 2018 – 2023. Clinical and demographic data were abstracted from the medical record, and specimens were processed for immune phenotyping by flow cytometry. Parametric and non-parametric statistics were used to analyze for associations with outcomes.


Results:

86% of patients were AJCC stage 3, 52% of tumors were located on the extremity, and 33% were retroperitoneal. 81% received preoperative radiotherapy, and the median BMI was 27 (range, 18.4 - 39.4). With a median follow up of 24.4 months, median metastasis free survival was 12.6 months (2.0 - 45.7), and median overall survival was 24.4 months (5.9 - 75.6). Overall, NK cells were approximately 55-fold more frequent in the blood (per mm3) than tumor (per mg, P< 0.05). The frequency of cytotoxic CD56dim NK cells of total NK cells was also greater in the blood than tumor (91.7% ± 5.35 blood vs. 82.4% ± 12.5 tumor, P = 0.0001). Increasing BMI was significantly associated with lower intratumoral NK cells (r = -0.46, P = 0.048) and lower intratumoral CD56dim NK cells (r = -0.51, P = 0.03). When stratifying by lean (BMI < 25) versus obese (BMI ≥ 30), lean patients had a greater proportion of CD56dim NK cells in the peripheral blood compared to obese (94.0% vs 89.4%, P = 0.014) as well as approximately 9-fold greater intratumoral CD56dim NK cells compared to obese (P = 0.02). When stratifying by the median BMI of 27, there was a trend for improved overall survival among lower BMI patients (P=0.08)


Conclusions:

Obesity is associated with differences in numbers and phenotype of NK cell infiltrates in STS patients undergoing surgery. Obesity-induced NK dysfunction may be prognostically relevant in STS.

Learning Objectives:

  • Upon completion, participant will be able to describe the differences between NK cell frequencies in peripheral blood versus tumor in soft tissue sarcoma.
  • Upon completion, participant will be able to describe the relationship between BMI and intratumoral NK cell populations.
  • Upon completion, participant will be able to describe the differences between NK cell frequencies in lean versus obese patients.