P37: Characterization of Natural Killer and Cytotoxic T Cell Immune Infiltrates in Pancreatic Ductal Adenocarcinoma

Friday, March 24, 2023

5:01 PM – 5:06 PM

Location: SSO HUB Pan-Tumor Zone: CRS, HPB, Pan-Tumor & Upper GI

Poster Presenter(s)

Julia Persky (she/her/hers)

Medical Student
UC Davis School of Medicine
Sacramento, California, United States

Disclosure information not submitted.

Author(s)

Julia Persky (she/her/hers)

Medical Student
UC Davis School of Medicine
Sacramento, California, United States

Disclosure information not submitted.
SC

Sylvia Cruz, BS

Medical Student
UC Davis School of Medicine, United States

Disclosure information not submitted.
Sean Judge, MD

Resident in Surgery
Department of Surgery, University of California, Davis
Sacramento, California, United States

Disclosure information not submitted.
CS

Cyrus Sholevar, MD

PGY-2 General Surgery Resident
UC Davis, United States

Disclosure information not submitted.
Sepideh Gholami, MD

Hepato-Pancreato-Biliary Surgeon
Northwell Health
Lake Success, New York, United States

Disclosure(s): No financial relationships to disclose
RB

Richard Bold, MD

Professor & Chief
Division of Surgical Oncology, Department of Surgery, UC Davis, United States

Disclosure information not submitted.
AK

Anthony Karnezis, MD, PhD

Associate Professor
Department of Pathology and Laboratory Medicine, UC Davis, United States

Disclosure information not submitted.
KM

Karen Matsukuma, MD, PhD

Assistant Professor
Department of Pathology and Laboratory Medicine, UC Davis, United States

Disclosure information not submitted.
MD

Morgan Darrow, MD

Assistant Professor
Department of Pathology and Laboratory Medicine, UC Davis, United States

Disclosure information not submitted.
RC

Robert J. Canter, MD

Division Chief, Surgical Oncology, Professor of Surgery
Department of Surgery, University of California Davis School of Medicine
Sacramento, California, United States

Disclosure information not submitted.

Disclosure(s):

Sepideh Gholami, MD: No financial relationships to disclose

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis and resistance to systemic therapies including immunotherapy. Although PDAC has been linked to low T cell infiltrate, the contribution of natural killer (NK) cells has received less attention. Our objective was to evaluate the immune parameters PDAC, including markers of NK cells, to determine if NK cells associate with patient outcomes.

Methods: We analyzed tumors from 93 PDAC patients treated from 2012 – 2020. Predictor variables included tumor infiltrating lymphocytes (TILs), T cell markers (CD3⁺, CD8⁺, CD45RO⁺), NK markers (NKp46) and NK inhibitory markers (TIGIT and MHC-I). TILs were scored from 0-3, and immune markers were scored from 0-300 by a blinded pathologist. We also evaluated neutrophil and lymphocyte levels in the blood. Primary outcome variables were progression-free survival (PFS) and overall survival (OS), analyzed by the Kaplan-Meier method.

Results: Mean age was 70, 55% were female, and the mean tumor size was 3.1±1.1cm. 89% involved the pancreatic head, and 63% were lymph node positive. The majority of patients received adjuvant therapy. With a median follow up of 24 months, median survival was 35 months. Blood lymphocytes levels prior to surgery were positively correlated with TILs (p=0.008 r=0.3). Median TILs infiltration was 1.1, and 50% were 0 or 1. Mean CD3⁺ score was 20.6±1, and mean NKp46 was 3.1±3.9. Although there was slight positive correlation between T cell and NK cell scores (CD3⁺/NKp46 p=0.005, r=0.3; CD8⁺/NKp46 p=0.05, r=0.2), neither T nor NK cell infiltration was associated with MFS or OS. Similarly, there was a tight positive correlation between MHC-I expression and all T cell markers (CD3⁺, CD8⁺ and CD45RO⁺), but not with NKp46 nor with survival outcomes (PFS/OS, P >0.05). TIGIT expression was also low (mean 30.8±21.9).

Conclusions: NK and T cell infiltrates are overall low in PDAC and do not associate with oncologic outcomes. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease. Strategies to increase MHC-I expression may be an effective way to stimulate a response to immunotherapy.

Learning Objectives:

Describe the tumor immune microenvironment of pancreatic cancer.
To understand the impact of TILs, NK cells, and T cells in pancreatic cancer outcomes.
To understand the relationship of MHC-I expression and NK cell infiltrates in pancreatic cancer.