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Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma

Ko, Jennifer S., MD, PhD*; Gastman, Brian R., MD; Conic, Ruzica, MD; Tellez Diaz Trujillo, Alejandra, MD; Diaz-Montero, Claudia Marcela, PhD; Billings, Steven D., MD*; Tarhini, Ahmad, MD, PhD§; Funchain, Pauline, MD§; Atanaskova Mesinkovska, Natasha, MD, PhD

The American Journal of Dermatopathology: March 2019 - Volume 41 - Issue 3 - p 180–187
doi: 10.1097/DAD.0000000000001286
Original Study

Introduction: Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome.

Materials and Methods: Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68+ tumor-associated macrophages, CD3+ tumor-infiltrating T cells, and PD-1+ activated/exhausted T cells; and hematolymphangiogenesis: CD31+/D2-40 blood vessels and D2-40+ lymphatics was performed by 2 blinded dermatopathologists.

Results: CB1Y tumors showed decreased CD3+ tumor-infiltrating T cells (P < 0.05) with significantly reduced PD1 expression (P ≤ 0.05). The CD3:PD1 ratio was higher in CB1Y (P < 0.05). Other tested parameters did not significantly differ between the 2 groups.

Discussion: As PD1 expression is induced during type 1 T-cell activation, these data suggest that immune ignorance or suppression may predominate in CB1Y. Further studies are required to identify interventions that may promote tumor-associated T-cell inflammation in such patients.

*Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH;

Dermatology and Plastic Surgery Institute, Cleveland Clinic, Cleveland, OH;

Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH;

§Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; and

Department of Dermatology, University of California, Irvine, Orange, CA.

Correspondence: Jennifer S. Ko, MD, PhD, Department of Pathology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (e-mail:

The authors declare no conflicts of interest.

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