Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg). MDSC levels have been shown to correlate negatively with prognosis and overall survival of patients with cancers of various types and stages. The role of MDSCs in cancer progression represents a promising target for effective cancer immunotherapy. In this review, we discuss the mechanisms of MDSC functions, their influence on tumor progression and metastasis, and finally focus on up to date nanoparticle approaches that target and antagonize MDSCs in tumor-bearing hosts. The development of multifunctional nanoparticle systems for effective imaging, assessment and manipulation of MDSCs will represent strategic theranostic innovations that may improve cancer staging, therapeutic outcomes, and overall patient survival.
Background
De-escalation of axillary surgery in breast cancer has progressively taken place when appropriate. Data supporting surgical de-escalation in patients with clinically node-positive (cN+) disease remains scarce. Here, survival among patients with cN+ T1–2 tumours undergoing sentinel lymph node biopsy (SLNB) and regional nodal irradiation (RNI) was investigated and compared with that among patients undergoing axillary lymph node dissection (ALND) with or without RNI.
Methods
The National Cancer Data Base was used to identify three groups of patients with cN+ tumours according to axillary management among those treated between 2010 and 2016: patients who underwent SLNB and RNI (cN+ SLNB/RNI group); those who had ALND and RNI (cN+ ALND/RNI group); and those who had ALND alone (cN+ ALND/no RNI group). Patients who underwent neoadjuvant chemotherapy, and those who had stage IV breast cancer or pN2–3 disease were excluded.
Results
A total of 12 560 patients met the inclusion criteria: 3030 in the cN+ SLNB/RNI, 5446 in the cN+ ALND/RNI, and 4084 in the cN+ ALND/no RNI group. The sizes of cN + SLNB/RNI and cN+ ALND/RNI groups increased over the study interval, whereas the cN+ ALND/no RNI group decreased in size (P < 0.001). There was a median of one positive node in the cN+ SLNB/RNI group and two nodes in the cN+ ALND/RNI and cN+ ALND/no RNI groups. The median number of nodes examined was three, 14, and 14, respectively (P < 0.001). Median follow-up was 57.9 (range 0.8–114) months. The overall survival rate was 97, 97, and 92 per cent respectively at two years, and 88, 86, and 78 per cent at five years (P < 0.001).
Conclusion
Patients with limited cN+ T1–2 breast cancer undergoing upfront SLNB and RNI have favourable survival outcomes that are not inferior to those of patients undergoing ALND with or without RNI. Prospective studies are warranted to assess locoregional control and long-term outcomes.
In Table 2 in the original online version of this article, the values for the variables Tumor Grade, Deleterious Mutations, and VUS listed under White should have been listed under Other groups and vice versa.
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