The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient survival, particularly in triple-negative and HER2-overexpressing BC subtypes. Although T cells are the predominant TIL population, the relationship between quantitative and qualitative differences in T cell subpopulations and patient prognosis remains unknown. We performed single-cell RNA sequencing (scRNA-seq) of 6,311 T cells isolated from human BCs and show that significant heterogeneity exists in the infiltrating T cell population. We demonstrate that BCs with a high number of TILs contained CD8 T cells with features of tissue-resident memory T (T) cell differentiation and that these CD8 T cells expressed high levels of immune checkpoint molecules and effector proteins. A CD8 T gene signature developed from the scRNA-seq data was significantly associated with improved patient survival in early-stage triple-negative breast cancer (TNBC) and provided better prognostication than CD8 expression alone. Our data suggest that CD8 T cells contribute to BC immunosurveillance and are the key targets of modulation by immune checkpoint inhibition. Further understanding of the development, maintenance and regulation of T cells will be crucial for successful immunotherapeutic development in BC.
The aims of our study were to examine the impact of PET in changing management in patients with proven or suspected colorectal cancer recurrence and to assess the impact of management change on disease-free survival. Methods: Symptomatic patients with a residual structural lesion suggestive of recurrent tumor (group A) or patients with pulmonary or hepatic metastases considered to be potentially resectable (group B) underwent PET scans. Pre-PET management plans were documented by referring clinicians unaware of the PET results, and follow-up to 12 mo was performed to determine actual management and clinical outcomes. Results: A total of 191 patients (118 men and 73 women; mean age, 66 y) were studied. PET detected additional sites of disease in 48.4% of patients in group A and in 43.9% of patients in group B. A change in planned management was documented in 65.6% of group A and in 49.0% of group B patients. These management plans were implemented in 96% of patients. Follow-up data in group A showed progressive disease in 60.5% of patients with additional lesions detected by PET, compared with conventional imaging, and in 36.2% of patients with no additional lesions detected by PET (P 5 0.04). In group B, progressive disease was identified in 65.9% of patients with additional lesions detected by PET and in 39.2% of patients with no additional lesions detected by PET (P 5 0.01). PET also provided valuable prognostic information on patients stratified into curative-or palliative-intent groups. Conclusion: These data demonstrate the significant impact of PET on management and outcomes in patients with suspected recurrent colorectal cancer.
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