QS15. Tumor-responsive natural killer cells infiltrate peritoneal metastasis from appendiceal adenocarcinoma

Thursday, March 5, 2026

10:15 AM - 10:19 AM MST

Location: Pan-Tumor HUB Zone

Primary Presenter(s)

Timothy P. McMullen, PhD (he/him/his)

Medical Student
University of California, Irvine
Orange, California, United States

Co-Author(s)

BG

Betul B. Gunes, MD, MS

Postdoctoral Scholar
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
KL

Kangyu Lin, PhD

Research Investigator
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
John P. Shen, MD (he/him/his)

Assistant Professor
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Michael G. White, MD, MS

Assistant Professor, Director of Research
Department of Colon and Rectal Surgery, University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Oliver S. Eng, MD (he/him/his)

Associate Professor of Surgery
University of California, Irvine
Orange, California, United States

Introduction: Peritoneal metastasis from appendiceal adenocarcinoma (PMAA) portends poor prognosis. PMAA is heavily infiltrated by several populations of adaptive immune cells, but the role of anti-tumor innate immunity in PMAA remains incompletely understood. Natural killer (NK) cells are innate cytotoxic lymphocytes which mediate robust anti-metastatic immunity in several cancer subtypes and have demonstrated prognostic relevance in human gastrointestinal cancers. We sought to investigate the role of NK cells in the human PMAA immune microenvironment.

Methods: To assess the response of NK cells to PMAA, we compared NK cells isolated from grade 1 and grade 2 PMAA in 4 human patients with NK cells isolated from tumor-naïve colorectal specimens using single-cell RNA sequencing (scRNA-seq). Differential gene expression analysis was performed using Seurat v5.

Results: NK cells are found in abundance in PMAA (Fig. 1A) and display several transcriptionally-distinct phenotypes (Fig. 1B). NK cells which express markers of terminal maturity and cytotoxic function, including NKp80 and IL2Rb, are enriched in PMAA relative to tumor-naïve colorectal mucosa (Fig. 1C). These enriched tumor-responsive NK cells co-express inhibitory NK cell markers, including CD94, KLRB1, and TGF-b—suggesting functional restriction which may limit NK cell-mediated anti-metastatic immunity in the peritoneum.

Conclusions: PMAA is associated with an NK cell response which may have therapeutic relevance. Tumor-infiltrating NK cells in PMAA express markers of functional activation and cytotoxicity, as well as inhibitory NK cell receptors—suggesting a nuanced role for infiltrating NK cells in the microenvironment of PMAA. Further investigation in this area will seek to uncover strategies for unleashing NK cell immunity in PMAA to potentially enhance metastatic control.

Learning Objectives:

Understand the role of NK cells in the response to PMAA as currently delineated in the literature
Understand phenotypic changes in NK cells prompted by infiltration into the microenvironment of PMAA