Systemic Immune Suppression Predicts Diminished Merkel Cell Carcinoma–Specific Survival Independent of Stage

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus/MCPyV). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune suppressed persons represent approximately 10% of the MCC patients, a significant over-representation relative to the general population. We hypothesized that immune suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1427 years (median 2.1 years). Immune suppressed persons (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared to persons with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, p < 0.01). Immune-suppressed persons thus have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be benefit of diminishing iatrogenic systemic immune suppression.

Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

“…In healthy individuals, infection with MCPyV is frequent [2]; however, additional factors, including loss of immune surveillance, are required for infection to result in MCC. Consistent with the notion that MCC has an immunologic basis, MCC is over-represented in immunocompromised patients, such as individuals with HIV or certain hematologic malignancies and organ transplant recipients, who collectively comprise approximately 10% of the MCC patient population [5,20]. Additionally, increased levels of intratumoral CD8 + T cells are associated with improved survival [21].…”

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

“…Immune suppression leads to a dramatically increased risk of developing MCC [5,7,8,31]. While 90% of MCC patients do not have clinically apparent immune dysfunction, patients on immunosuppressive regimens following organ transplantation or with compromised cell-mediated immunity (such as those with chronic lymphocytic leukemia and HIV/AIDs) are 10-30-fold more likely to develop MCC and suffer a higher MCC-specific mortality rate than the general population [5,[31][32][33][34].…”

“…The majority of MCCs are associated with the Merkel cell polyomavirus (MCPyV) MCC occurs more frequently in patients with immunodeficiency, including AIDS, suggesting that MCC may have an infectious etiology similar to Kaposi's sarcoma and EBV-induced Burkitt's lymphoma [7][8][9][10]. This was confirmed in 2008 when MCPyV was discovered in eight of ten MCC tumors using Digital Transcriptome Subtraction, a high-throughput cDNA sequencing platform that aligned MCC tumor Rationale for immune-based therapies in Merkel polyomavirus-positive and -negative Merkel cell carcinomas future science group Review Vandeven & Nghiem transcripts against reference human sequences [6].…”

Human Merkel cell polyomavirus: virological background and clinical implications

“…Factors recognized as associated with poor prognosis are size of the tumor and presence of metastases according to the AJCC staging (4,47,55,(64)(65)(66)(67)(68), and immunosuppression (65,69,70). Recently, histological and immunochemistry markers have been described as potentially associated with poor outcome like low tumor infiltrating CD8 + T cells (101) and P53 and P63 expression and gen mutations (54, 68, 74) ( Table 2).…”