Immune phenotype predicts risk for posttransplantation squamous cell carcinoma

Area of Science:

• Immunology
• Transplantation Medicine
• Dermatology

Background:

• Kidney transplant recipients (KTRs) have a high incidence (up to 30%) of cutaneous squamous cell cancer (SCC) within 10 years.
• Current clinical methods lack reliability in predicting multiple SCC development in KTRs.
• Elevated regulatory T cell counts correlate with poor prognosis in general cancer patients, suggesting potential as SCC predictors in KTRs.

Purpose of the Study:

• To identify predictive markers for cutaneous SCC development in kidney transplant recipients.
• To investigate the association between immune cell profiles and SCC incidence in KTRs.
• To compare immune cell markers in SCC from KTRs versus non-KTRs.

Main Methods:

• A case-control study matched KTRs with (n=65) and without (n=51) SCC for gender, age, and immunosuppression duration.
• Risk factors for incident SCC were assessed during a median follow-up of 340 days.
• Peripheral blood immune cell counts (FOXP3(+)CD4(+)CD127(low) regulatory T cells, natural killer cells) and tumor CD8/FOXP3 expression ratios were analyzed.

Main Results:

• High peripheral FOXP3(+)CD4(+)CD127(low) regulatory T cells (>35/microl), low natural killer cells (<100/microl), and prior SCC history significantly increased SCC risk (HRs 2.48, 5.6, 1.33 respectively).
• A lower CD8/FOXP3 expression ratio in excised SCC from KTRs (n=25) compared to non-KTRs (n=25) was observed.
• This lower CD8/FOXP3 ratio was associated with the development of new cutaneous SCCs.

Conclusions:

• Immune system monitoring, specifically regulatory T cell levels and CD8/FOXP3 ratios, can predict cutaneous SCC development in KTRs.
• These immune markers offer potential for improved risk stratification and early detection of SCC in this vulnerable population.
• Further research into immune modulation could inform strategies for SCC prevention in KTRs.