Gastrointestinal Cancer

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SU_3_2028 - The Immune Milieu of Anal Squamous Cell Carcinoma: IDO Expression is Correlated With Poor Outcome

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

The Immune Milieu of Anal Squamous Cell Carcinoma: IDO Expression is Correlated With Poor Outcome
D. Mitra1, N. Horick2, D. Brackett2, K. Mouw3, J. Hornick3, S. Ferrone2, T. S. Hong4, H. J. Mamon5, J. W. Clark2, A. S. Parikh2, D. P. Ryan2, V. Deshpande2, and J. Y. Wo6; 1Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Boston, MA, 5Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, 6Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Purpose/Objective(s): Characterization of the tumor immune microenvironment improves our understanding of cancer oncogenesis and may suggest novel avenues for therapeutic intervention. The current study examines a panel of 5 immune markers in pre-treatment, localized ASCC, including 2 markers which have not previously been studied in ASCC: (1) indoleamine 2,3 dioxygenase 1 (IDO1), a tryptophan metabolizing enzyme associated with immune tolerance, and (2) HLA class I, the cell surface complex responsible for antigen presentation on tumor cells.

Materials/Methods: Retrospective review identified patients with localized ASCC at two large cancer centers who met the following criteria: (1) received definitive chemoradiation between 2001-2016, (2) had pre-treatment tissue locally available, and (3) had >5 months of follow-up. Immunohistochemistry (IHC) for the immune markers CD8 (4B11), PD-1 (EH33), PD-L1 (E1L3N), HLA class I (HC10) and IDO (D5J4E) was performed and scored by two pathologists. Univariate and multivariate Cox proportional hazards models were used to evaluate associations between outcomes and immune markers, controlling for clinical characteristics.

Results: Sixty-three ASCC patients met enrollment criteria with the following distribution by stage: I-11%, II-38%, IIIA-13%, IIB-33%, unknown-5%. Thirty percent had HIV or were on an immunosuppressive medication at the time of diagnosis. Immune marker expression within the tumor varied substantially among patients with the following median and range: CD8+ T cells-78/hpf (0-782/hpf); PD-1+ cells-17/hpf (0-178/hpf); PD-L1+ tumor cells-1% (0-75%); HLA class I + tumor cells-100% (0-100%); and IDO+ tumor cells- 1% (0-100%). Median follow-up from the start of radiation was 35 months (range excluding 2 patients who died during treatment: 5-145 months). On both univariate and multivariate analyses >50% of tumor cells being IDO+ was associated with worse overall survival (HR 4.7, 95% CI 1.5-14.6, p=0.007) and higher likelihood of recurrence (HR 6.4, 95% CI 2.0-20.1, p=0.002) including both local recurrence (HR 8.6, 95% CI 2.6-29.1, p=0.0005) and distant metastasis (HR 12.7, 95% CI 3.3-49.2, p=0.0002). Tumors with >50% IDO positivity were significantly more likely to have the lowest quartile of CD8+ tumor infiltrating lymphocytes (TIL, <40/hpf) (p=0.024). While there were no robust associations between the other immune markers and outcome, patients with more CD8+ TIL tended to have more PD-1+ cells (R=0.47, p=0.0006) as well as more PD-L1+ tumor cells (R=0.36, p=0.04) suggesting a subset of ASCC patients have a pre-existing population of exhausted immune cells in the microenvironment.

Conclusion: ASCC has a diverse immune milieu. While patients generally do well with standard therapy, IDO may serve as a prognostic indicator of poor outcome and could help identify a patient population who might benefit from IDO-targeted therapies.

Author Disclosure: D. Mitra: None. N. Horick: None. D. Brackett: None. K. Mouw: None. J. Hornick: None. T.S. Hong: Research Grant; Taiho, Novartis. H.J. Mamon: Honoraria; Up to Date. V. Deshpande: None.

Devarati Mitra, MD, PhD

Disclosure:
No relationships to disclose.

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