Results of a retrospective study suggest that high indoleamine 2,3 dioxygenase 1 (IDO1) expression in tumor is a negative prognostic marker for patients with localized anal cancer. This study was published online in the Oncologist.

Although the incidence of anal cell squamous carcinoma (ASCC) has been rising for many years, definitive chemoradiation has remained the standard-of-care treatment for patients with localized disease for more than 3 decades.

Nevertheless, approximately one-fourth of patients with more advanced localized disease treated with chemoradiation will not be cured. Hence, novel biomarkers, particularly those associated with immunosuppression of the tumor microenvironment, are being sought to aid in the identification of patients who are likely to benefit from other treatment approaches. 

The study involved an assessment of clinical outcomes and tumor-based characteristics of 63 patients with nonmetastatic ASCC treated with definitive chemoradiation at Massachusetts General Hospital Cancer Center and Brigham & Women’s Hospital/Dana-Farber Cancer Center Institute, Boston, Massachusetts, between 2005 and 2016. Pretreatment tumor specimens were available for all patients included in the analysis, and immunohistochemical testing of the following immune biomarkers was performed: CD8; PD-1; PD-L1; IDO1; and human leukocyte antigen (HLA) class I.  Median follow-up was 35 months.

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The key finding from the study was the significant association between a high level of IDO1 expression in tumor and poor overall survival. In patients for whom at least 50% of tumor tumors expressed IDO1, hazard ratios were 4.7 (P =.007), 8.6 (P =.0005), and 12.7 (P =.0002) for increased risk of death, local recurrence, and distant metastasis, respectively, compared with patients who had tumors with lower levels of IDO1 expression. In addition, tumors with at least 50% IDO1 expression were more likely to have low levels of CD8 infiltrate (P =.024). None of the other tumor immune biomarkers tested was significantly associated with clinical outcome.

“Given that our study has shown the dismal prognosis of patients with high tumor IDO1 levels, as well as the association of high IDO1 level with the lowest quartile of CD8+ tumor infiltrating lymphocytes, it seems likely that anti-PD-1 therapy may not be sufficient in treating patients with ASCC with high IDO1. Rather, this study suggests that IDO1-targeted therapies may have an important role in IDO1-high ASCC, either in the metastatic setting or, given the very short time to disease recurrence in patients with IDO1-high primary tumors, in the adjuvant setting after definitive chemoradiation,” the authors wrote in conclusion.

Reference

  1. Mitra D, Horick NK, Brackett DG, et al. High IDO1 expression is associated with poor outcome in patients with anal cancer treated with definitive chemoradiotherapy [published online February 12, 2019]. Oncologist. doi: 10.1634/theoncologist.2018-0794