Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs.

Relationship between PD-L1 expression and clinical characteristics in patients with breast invasive ductal carcinoma

ObjectiveTo evaluate the expression of PD-L1 (programmed death 1 ligand 1, PD-L1) and its clinical significance in breast invasive ductal carcinoma.MethodsTumor samples were collected from 64 cases of breast invasive ductal carcinoma patients, and tumor adjacent normal breast tissue were obtained as normal control. The expression of PD-L1 were examined by immunohistochemical staining and real time PCR assay, its correlations with patients’ clinical pathological characteristics were analyzed.ResultsPD-L1 was found to be over-expressed in 24 of 64 (37.5%) breast invasive ductal carcinoma samples, while in 1 of 22 (4.5%) tumor adjacent normal breast tissue which indicated PD-L1 was higher expressed in breast invasive ductal carcinoma samples than the tumor adjacent normal breast tissue (P < 0.05). PD-L1 positive expression was associated with clinical pathological characteristics of TNM stage and pathology grading (P < 0.05). However, PD-L1 positive expression was not correlated with age (P > 0.05), menstruation status (P >0.05), family history of breast cancer (P > 0.05), tumor diameter (P > 0.05), lymph node metastasis (P > 0.05) and tumor location (P > 0.05).ConclusionPD-L1 may play an important role in invasive ductal carcinoma, which could be a potential indicator for advanced clinical stage and poor prognosis.

Pttg1 Promotes Growth of Breast Cancer through P27 Nuclear Exclusion

Background/Aims: A role of Pituitary Tumor Transforming Gene 1 (Pttg1) in the carcinogenesis has been shown in some cancers, but not in BC (BC). Methods: We compared the levels of Pttg1 in the resected BC tissue with the adjacent normal breast tissue from the same patient. We modified Pttg1 levels in a BC cell line, MCF7, by either a Pttg1 transgene, or a Pttg1 shRNA. The cell growth was measured in an MTT assay. The cell apoptosis was measured by apoptosis assay. The nuclear protein of cell-cycle-related genes was examined in Pttg1-modifed BC cells. Co-immunoprecipitation was performed to examine the association of Pttg1 and p27. Results: We detected significantly higher levels of Pttg1 in the resected BC tissue, compared to the adjacent normal breast tissue from the same patient. Overexpression or depletion of Pttg1 in MCF7 significantly increased or inhibited cell growth, respectively. Changes in Pttg1 levels, however, did not alter cell apoptosis, suggesting that Pttg1 increases cell growth through augmented cell proliferation, rather than decreased cell apoptosis. Among all examined cell-cycle-related proteins in Pttg1-modifed BC cells, only nuclear p27 levels were significantly affected. Further, co-immunoprecipitation showed that Pttg1 directly associated with p27. Conclusion: Pttg1 may increase BC cell growth through nuclear exclusion of p27, which highlights a novel molecular regulatory machinery in tumorigenesis of BC.