69: Peritoneal fluid cytokine analysis reveals targets for regional immunotherapy in carcinomatosis

Saturday, March 25, 2023

8:42 AM – 8:52 AM

Location: Ballroom B

Abstract Presenter(s)

Chelsea Knotts, MD

Surgical Oncology Fellow
Allegheny Health Network
Pittsburgh, Pennsylvania, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

Chelsea Knotts, MD

Surgical Oncology Fellow
Allegheny Health Network
Pittsburgh, Pennsylvania, United States

Disclosure(s): No financial relationships to disclose

Author(s)

VD

Vera Donnenberg, PhD

Scientist
University of Pittsburgh Medical Center, United States

Disclosure information not submitted.
CC

Christian Cruz Pico, MD

Fellow
Allegheny Health Network Cancer Institute, United States

Disclosure information not submitted.
SS

Suzanne Schiffman, MD

Attending Surgeon
Allegheny Health Network Cancer Institute, United States

Disclosure information not submitted.
WN

William Nelson, MD

Attending Surgeon
Allegheny Health Network, United States

Disclosure information not submitted.
KN

Kirsten Newhams, MD

Attending Surgeon
Allegheny Health Network, United States

Disclosure information not submitted.
Casey J. Allen, MD

Assistant Professor, Division of Surgical Oncology
Allegheny Health Network
Pittsburgh, Pennsylvania, United States

Disclosure(s): No financial relationships to disclose
AD

Albert Donnenberg, PhD

Scientist
University of Pittsburgh Medical Center, United States

Disclosure information not submitted.
David L. Bartlett, MD

System Chair
Allegheny Health Network Cancer Institute
Pittsburgh, Pennsylvania, United States

Disclosure information not submitted.
Patrick Wagner, MD

Director, AHN Cancer Institute Division of Complex General Surgical Oncology
Allegheny Health Network
Pittsburgh, Pennsylvania, United States

Disclosure(s): No financial relationships to disclose

Disclosure(s):

Chelsea Knotts, MD: No financial relationships to disclose

Casey J. Allen, MD: No financial relationships to disclose

Patrick Wagner, MD: No financial relationships to disclose

Introduction: The peritoneal cavity, as a potential space, constitutes a fluid phase tumor microenvironment that is poorly defined. Characterization of this environment could identify targets for regional immunotherapy in carcinomatosis. We examined peritoneal fluid and serum cytokine levels to identify such targets.

Methods: Patients with (n=15) or without (n=24) carcinomatosis undergoing laparoscopy were consented for a biomaterial collection protocol in which peritoneal fluid, serum and parietal peritoneal tissue were obtained. Peritoneal fluid was obtained either via peritoneal washings (500cc volume, n=13), or via absorption onto surgical sponges followed by elution into analytic buffer (n=36). Cytokine concentrations obtained using the Luminex 38-plex panel plus IL6Rα and TGFβ (40 total analytes) were compared among subgroups using the Mann-Whitney U test (Bonferroni corrected for multiple comparisons). Correlation among collection techniques (serum, fluid washings and sponge absorption) was performed using linear regression.

Results:

Fibroblast growth factor-2 (FGF-2) and the soluble IL-6 receptor a subunit (IL-6ra) were the most highly concentrated analytes in peritoneal fluid with or without carcinomatosis. IL6, the cognate ligand for IL6-ra, showed a 21.2-fold increase in mean concentration in samples from patients with carcinomatosis vs. without (p=0.01), making it the most highly concentrated analyte in patients with carcinomatosis. Additional analytes with significant elevations in carcinomatosis included TGF-b (30-fold increase, p=0.004), MCP1 (5.6-fold increase, p=0.04), MIP1b (6.1-fold, p=0.04) and Eotaxin (68.5-fold, p=.04). Correlation was generally poor between paired serum and peritoneal fluid concentrations across analytes, including IL-6 (r=0.26; p=0.27). This suggests an active, cavity-specific process leading to elevated IL6 levels. Findings from peritoneal washings largely recapitulated those from absorbed peritoneal fluid for high concentration analytes only, presumably due to dilution effects inherent in the procedure.

Conclusions: IL6rα and FGF2 are highly concentrated in peritoneal fluid, with or without carcinomatosis. In carcinomatosis, an exponential increase in IL6 concentration was seen, illuminating this pathway as a target ripe for therapeutic intervention. Based on this work, clinical trials are planned to examine targeted IL6-rα inhibitors (tocilizumab) and FGF pathway antagonists, in order to explore their immunomodulatory effects as single agents or in combination with other novel immunotherapeutic regimens.

Learning Objectives:

Upon completion, participant will be able to describe the rationale for cytokine assessment in peritoneal cavity immunotherapy.
Upon completion, participant will be able to name key cytokines over-represented in peritoneal fluid.
Upon completion, participant will be able to name pathways for potential immunotherapy in peritoneal surface malignancy.