1587P - Tumor infiltrating lymphocytes and tertiary lymphoid structures in paired primary tumors and metastases from breast cancer patients

Abstract

In primary tumors (P), infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS) have been associated with better clinical outcomes, in HER2+ and triple negative breast cancer (BC). The temporal and spatial heterogeneity of TIL and TLS between P and their matched metastases (M) is currently unknown. We analyzed formalin fixed paraffin embedded tissue samples from a retrospective cohort of BC patients who underwent adjuvant surgery for the P and metastasectomy or biopsy for their metachronous M at a distant site(s) (n = 51). Immunohistochemistry stained sections using anti-CD3 (T cells) and anti-CD20 (B cells) antibodies in a double stain were scored by two trained pathologists blinded to the clinical data. TIL were scored as the percent (%) of stroma plus tumor surface area infiltrated with CD3+ plus CD20+ cells. The number of TLS were normalized to the tumor area. The extent of TIL in P (range 1-35%) was significantly higher with respect to the corresponding M (p = 0.04). Interestingly, when the extent of TIL in P was ≥10% (=TIL+) there was a significant decrease in the %TIL detected in M (p < 0.0001, n = 20). Alternatively, when TIL infiltration in the P was <10% (=TIL-) the %TIL was significantly higher at the distant M site (p = 0.002, n = 31). In secondary M lesions, TIL varied between 0-20% and TLS were essentially absent. Analysis of TIL in M from different organs revealed a significantly higher level in soft tissues (n = 4) compared to skin (n = 24), brain (n = 2) or breast relapses (n = 14) (p = 0.04). These preliminary data suggest that tumors can alter their immunogenicity during disease progression by their production of neoantigens and/or immunosuppressive factors, which potentially accounts for our observed differences between P and M. In metastatic disease, the extent of immune infiltration is globally lower than in early disease with almost no TLS found in M, signifying that the composition and organization of the immune infiltrate varies between disease stages. The extent of the immune infiltrate may also depend upon the organ site of relapse, further complicating the heterogeneity of both the tumor and the anti-tumor immune response.