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Immunology and Immunotherapy

(P 245) SUBTYPE SPECIFIC CHARACTERIZATION OF IMMUNE INFILTRATION IN SOFT TISSE SARCOMAS

    Author(s)

  • Sylvia M. Cruz, MD (she/her/hers)

    Resident Physician
    Surgical Oncology, Department of Surgery, University of California, Davis
    Sacramento, California, United States

    • Co-Author(s)

  • Sean J. Judge, MD, MS

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

  • MD

    Morgan A. Darrow, MD

    Associate Clinical Professor
    Pathology and Laboratory Medicine, University of California, Davis
    Sacramento, California, United States

  • Cyrus J. Sholevar, MD

    Resident Physician
    Surgical Oncology, Department of Surgery, University of California, Davis
    Sacramento, California, United States

  • ML

    Marshall Lammers, BS

    mlammers@ucdavis.edu
    Sacramento, California, United States

  • AM

    Arta M. Monjazeb, MD, PhD

    Radiation Oncology, University of California, Davis
    Sacramento, California, United States

  • WM

    William J. Murphy, PhD

    Department of Dermatology, University of California, Davis
    Sacramento, California, United States

  • Robert J. Canter, MD

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

Objective: Intratumoral natural killer (NK) cells have been linked with favorable outcomes in soft tissue sarcoma (STS) patients, but data assessing immune heterogeneity across the over 50 different STS histologic subtypes and associations with clinical outcomes are lacking.

Methods: We evaluated archived tumor tissue from 83 patients with resectable STS from 2007-2022. Immune markers were analyzed by immunohistochemistry, including tumor infiltrating lymphocyte (TIL) score (0-3) and H-scores (0-300) for CD3, CD8, and NKp46. Primary outcome variables were metastasis-free survival (MFS) and overall survival (OS). Multivariate analysis was performed using a Cox proportional hazards model, adjusting for age, sex, histologic type, and tumor size.

Results: Among our cohort, the mean age was 64 years and 57% were male. Mean tumor size was 12.5 cm and 88% were high grade, consistent with a high-risk population. 64% were located on the extremity, 20% retroperitoneal, and 16% trunk. Histologies included undifferentiated pleomorphic sarcoma (UPS) (25%), myxofibrosarcoma (25%), liposarcoma (24%), synovial sarcoma (9%), leiomyosarcoma (7%), and other (10%). 75% of the liposarcomas were dedifferentiated liposarcoma. Immune infiltrates were overall low across histologies with mean TIL score of 1.03±0.83. Synovial sarcoma had the lowest mean TIL score compared to myxofibrosarcoma, UPS, and dedifferentiated liposarcoma (P < 0.05). We observed the greatest expression of both CD3 and NKp46 in UPS (27.5±7.4 and 8.8±5.2, respectively) as compared to the lowest CD3 in synovial sarcoma (3.3±1.3, P< 0.05) and lowest NKp46 in leiomyosarcoma (0±0, P=0.06). On univariate analysis, CD3, CD8, and NKp46 expression were all positively associated with improved OS, but on multivariate analysis, only NKp46 expression was independently associated with significantly improved OS (P=0.04) for all histologic subtypes.

Conclusion: Despite variability in extent of immune infiltration, NK cell infiltration is associated with improved survival across STS histologies. These data support intratumoral NK cells as a biomarker for both prognosis and improving immunotherapy approaches in STS.