Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity.

Breast cancers regroup many heterogeneous diseases unevenly responding to currently available therapies. Approximately 70-80% of breast cancers express hormone (estrogen or progesterone) receptors. Patients with these hormone-dependent breast malignancies benefit from therapies targeting endocrine pathways. Nevertheless, metastatic disease remains a major challenge despite available treatments, and relapses frequently ensue. By improving patient survival and quality of life, cancer immunotherapies have sparked considerable enthusiasm and hope in the last decade but have led to only limited success in breast cancers. In addition, only patients with hormone-independent breast cancers seem to benefit from these immune-based approaches. The present review examines and discusses the current literature related to the role of hormone receptor signaling (specifically, an estrogen receptor) and the impact of its modulation on the sensitivity of breast cancer cells to the effector mechanisms of anti-tumor immune responses and on the capability of breast cancers to escape from protective anti-cancer immunity. Future research prospects related to the possibility of promoting the efficacy of immune-based interventions using hormone therapy agents are considered.

Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers.

Breast cancers are commonly associated with an immunosuppressive microenvironment responsible for tumor escape from anti-cancer immunity. Cells of the myeloid lineage account for a major part of this tumor-promoting landscape. These myeloid cells are composed of heterogeneous subsets at different stages of differentiation and have traditionally been described by their cardinal ability to suppress innate and adaptive anticancer immunity. However, evidence has accumulated that, beyond their immunosuppressive properties, breast cancer-induced myeloid cells are also equipped with a broad array of "non-immunological" tumor-promoting functions. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. We herein analyze and discuss current literature related to the versatile properties of the different myeloid cell subsets engaged in breast cancer development. We critically assess persisting difficulties and challenges in unequivocally discriminate dedicated subsets, which has so far prevented both the selective targeting of these immunosuppressive cells and their use as potential biomarkers. In this context, we propose the concept of IMCGL, "pro-tumoral immunosuppressive myeloid cells of the granulocytic lineage", to more accurately reflect the contentious nature and origin of granulocytic cells in the breast tumor microenvironment. Future research prospects related to the role of this myeloid landscape in breast cancer are further considered.

Influence of the Metabolism on Myeloid Cell Functions in Cancers: Clinical Perspectives.

Tumor metabolism plays a crucial role in sustaining tumorigenesis. There have been increasing reports regarding the role of tumor metabolism in the control of immune cell functions, generating a potent immunosuppressive contexture that can lead to immune escape. The metabolic reprogramming of tumor cells and the immune escape are two major hallmarks of cancer, with several instances of crosstalk between them. In this paper, we review the effects of tumor metabolism on immune cells, focusing on myeloid cells due to their important role in tumorigenesis and immunosuppression from the early stages of the disease. We also discuss ways to target this specific crosstalk in cancer patients.

Local and Metastatic Relapse Features in Patients After a Primary Soft Tissue Sarcoma: Advocating for a Better-Tailored Follow-Up.

Background: No consensus exists on how to follow patients after complete remission of a primary Soft Tissue Sarcoma (STS). Studying relapse features could help tailor guidelines for follow-up. Patients and Methods: Patients in complete remission after initial management of a localized STS at Institut Bergonié who presented a first local and/or metastatic relapse between January 1995 and July 2015 were eligible. Characteristics of relapse diagnosis were retrospectively collected. Results: 359 patients met inclusion criteria. 197 and 187 patients presented a local relapse and a metastatic relapse, respectively. In group 1 (limbs/trunk wall) and 2 (trunk/gynecological/other location), local relapse was diagnosed on clinical symptoms in 89 and 44% of cases, first detected by the patient himself in 68.5 and 34% of cases, and outside a planned visit in 67 and 36% of cases, respectively. In patients with metastatic relapse, diagnosis was made during a planned visit in 63% of cases, and by imaging in 62% of cases. Median survival after relapse was not different whether the first local relapse was diagnosed clinically or by imaging (44 [95%CI: 28-69.8] vs. 57 months [95%CI: 33.9-84.5], p = 0.35) but was longer if diagnosis of metastatic relapse was made on planned chest-CT scan rather than chest X-ray (58 [95%CI: 35.5-103.9] vs. 25 months [95%CI: 16.5-32.6], p < 0.05). Conclusion: Patient's education for regular clinical examination can be recommended for follow-up of local relapses after a primary STS of the limbs or superficial trunk. Modeling studies aiming at better understanding and predicting tumor biology to improve tailoring STS patients' follow-up are warranted.

Sarcoidosis-like reaction in metastatic triple negative breast cancer treated by anti-PD-L1.

We report the first case of sarcoidosis-like reaction in a patient treated by anti-PD-L1 for a breast cancer. A 69-year-old woman presented with a histologically confirmed lung metastasis of a triple negative breast cancer. She was treated by nab-paclitaxel plus anti-PD-L1 in first line. After 2 months, a dramatic lung response was noticed but an involvement of mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epitheloid granulomas without caseating necrosis in favour of a sarcoidosis-like reaction. The patient remained free of symptom and in complete lung response on anti-PD-L1 treatment as a maintenance therapy.