Carpen Laura, Falvo Paolo, Orecchioni Stefania, Mitola Giulia, Hillje Roman, Mazzara Saveria, Mancuso Patrizia, Pileri Stefano, Raveane Alessandro, Bertolini Francesco
Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Milan, Italy.
Human Technopole, Milan, Italy.
Cell Death Discov. 2022 Mar 8;8(1):106. doi: 10.1038/s41420-022-00893-x.
Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumor microenvironment (TME) of two TNBC mouse models has been performed using single-cell RNA sequencing technology. Specifically, immune cells were evaluated in untreated conditions and after treatments with chemotherapy or immunotherapy used as single agents or in combination. A decrease of Treg was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy and an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were enriched in treatments with low efficacy while M1-like macrophages followed an opposite trend. For both models, similar proportions of B cells were detected with an increase of proliferative B cells in treatments involving cisplatin in combination with αPD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC.
乳腺癌（BC）是全球主要的健康问题，是女性中最常见的恶性肿瘤。目前BC的治疗方案主要取决于组织学类型、分子标志物、临床侵袭性和疾病分期。免疫疗法，如αPD-1，已显示出与化疗联合在三阴性乳腺癌（TNBC）中的临床活性，表明某些治疗组合比其他组合更有效。然而，从未有人对这些治疗中涉及的主要免疫细胞群体进行过清晰的概述。在此，使用单细胞RNA测序技术对两种TNBC小鼠模型的肿瘤微环境（TME）中的免疫格局进行了评估。具体而言，在未治疗的条件下以及在用化疗或免疫疗法作为单一药物或联合使用后的条件下对免疫细胞进行了评估。在具有体内疗效的治疗中发现调节性T细胞（Treg）减少，γδT细胞也减少，γδT细胞在小鼠中具有促肿瘤活性。聚焦于细胞毒性T淋巴细胞（Cd8 T细胞），在所有条件下，在疗效较低的临床前治疗中证实了耗竭样Cd8 T细胞普遍增加，而增殖性Cd8 T细胞则呈现相反的趋势。关于巨噬细胞，M2样细胞在疗效较低的治疗中富集，而M1样巨噬细胞则呈现相反的趋势。对于两种模型，检测到相似比例的B细胞，在涉及顺铂与αPD-1联合的治疗中增殖性B细胞增加。这项工作中对免疫TME的精细表征可为TNBC的诊断和治疗带来新的见解。
