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Lower Number of CD3+ T-Lymphocytes Associated with Higher Risk of cSCC Metastasis


Metastatic cSCC cases were found to less likely have infiltration by CD3+ lymphocytes in intratumoral, stromal, or peritumoral regions. Fewer brisk or absent intratumoral densities of FOXP3+ tumor-infiltrating lymphocytes were found in cases as compared to controls.

Clinical Pearls

  • This matched case-control study aimed to determine if there is any association between type and density of tumor-infiltrating lymphocytes (TILs) and risk of metastasis in cutaneous Squamous Cell Carcinoma (cSCC)

  • Cases were defined as cSCC that metastasized to at least 1 lymph node or organ and controls were cSCC which did not metastasize at all. 30 cases and 30 controls were included, and all cases were matched to controls based on age, sex, immune status, tumor location, and BWH cSCC staging.

  • Metastatic cSCC cases were found to less likely have infiltration by CD3+ lymphocytes in intratumoral, stromal, or peritumoral regions. Fewer brisk or absent intratumoral densities of FOXP3+ tumor-infiltrating lymphocytes were found in cases as compared to controls.


Discussion:

In this study, Ashrafzadeh et al. study the association between type, location, and density of tumor-infiltrating lymphocytes (TILs) in metastatic primary cutaneous squamous cell carcinoma (cSCC) as compared to non-metastatic cSCCs. The authors cited past studies showing intratumoral T-lymphocyte infiltration was associated with good clinical outcomes in melanoma and Merkel cell carcinoma, however, no studies had yet been completed investigating this association with cSCC.


Using a case-control design, the authors defined cases as cSCCs which had metastasized to at least 1 lymph node or organ while controls were defined as cSCCs which had no metastasis at all. Cases were then matched to controls based on age, sex, immune status, tumor location, and Brigham and Women’s Hospital cSCC staging. Tumor specimens underwent immunohistochemical stains for CD3, CD4, CD8, and FOXP3+ cells.

60 total tumor specimens were analyzed (30 cases and 30 controls), with most of them occurring on the head and neck (66.7%) and at stage T2a (46.7%). Cases were found to be less likely to have infiltration by CD3+ lymphocytes in peritumoral, stromal, or intratumoral regions. Cases were also found less likely to have brisk (26.7% vs 6.7%; p=0.03) and absent (23.3% vs 13.3%; p=0.03) TIL density of FOXP3+ regulatory T-lymphocytes intratumorally. No differences in location or density of CD4+ or CD8+ T-lymphocytes were found when comparing cases to controls. Although this study is limited by its small sample size, it provides valuable data on patterns of tumor-infiltrating lymphocytes in cSCC.

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