Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment (TME) of colorectal cancer (CRC) patients, compared to blood from healthy donors (HDs) and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of cells expressing myeloid markers and lacking the expression of major histocompatibility complex class II molecule HLA-DR in blood and tumor of CRC patients. Further analysis revealed that these cells were granulocytic and expressed Arginase 1 indicative of their suppressive phenotype. These expanded cells could be neutrophils or granulocytic MDSCs, and we refer to them as granulocytic myeloid cells (GMCs) due to the phenotypical and functional overlap between these cell subsets. Interestingly, the expansion of peripheral GMCs correlated with higher stage and histological grade of cancer, thereby suggesting their role in cancer progression. Furthermore, an increase in CD33+CD11b+HLA-DR−CD14−CD15− immature myeloid cells was also observed in CRC tumor tissue. Our work shows that GMCs are expanded in circulation and TME of CRC patients, which provides further insights for developing immunotherapeutic approaches targeting these cell subsets to enhance antitumor immune and clinical responses.

Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-017-1977-z) contains supplementary material, which is available to authorized users.

Acute lymphoblastic leukemia (ALL) is a relatively rare lymphoid disorder with approximately 11 cases per million persons per year in United States. It is seen more commonly in children however adults are also affected with the median age approximately 39 years. The prognosis is influenced by the age of the patient and genetic findings. Abnormal cytogenetic is present in approximately 80 % of the patients. Philadelphia chromosome t (9;22) is seen in approximately 30 % of adult patients (Ph + ALL) and imparts a poor prognosis. Allogeneic stem cell transplant remains one of the corner stones of therapy along with Tyrosine Kinase Inhibitors TKIs (Imatinib or Dasatinib). Patients who are unable to go for transplant are kept on TKIs and continue consolidation and maintenance chemotherapy. In this retrospective review, we present patients with Philadelphia chromosome positive ALL seen at our institute and their outcomes. Tumor registry data base was searched for adult patients with ALL between January 1st 2010 and June 30th 2015. Forty patients were identified with B cell ALL and ten patients were diagnosed with Ph+ ALL (25 % of the cohort). The median age was 30 years (range 18 - 73 years). Male to female ratio was 4.5:1 Induction therapy was given based on UK ALL protocol. Tyrosine kinase inhibitor (Imatinib) was added when information regarding BCR-ABL translocation status was available. Interestingly 8 out of the 10 Ph+ patients also had CD 20 positive disease and were treated with rituximab in addition to standard chemotherapy and TKI. Two patients were lost from follow-up after receiving initial therapy and achieving remission. Four patients had HLA identical siblings and were able to go for allogeneic stem cell transplant. With a median follow up of 28 months (range 1 to 57 months), 3 of the 4 patients are alive and in complete molecular remission. One patient relapsed 19 months post-transplant and died of complications of a 2nd transplant. The remaining 4 patients were unable to go for allogeneic stem cell transplant. They were treated with Hyper-CVAD regimen and Dasatinib (Rituximab was used in patients with CD 20 positive clone). One patient died of colitis and relapsed ALL (36 months post diagnosis) while the other 3 patients are alive and on active therapy, all being in complete molecular remission. Discussion: This is the first report of incidence, management and outcome of Ph+ ALL from UAE. Ph + ALL contribute to 25 % of the cohort of ALL patients in our center. Majority of this cohort was also CD 20 positive. All patients achieved a complete hematologic remission after induction therapy. However, less than half of the patients were able to go for allogeneic stem cell transplantation as consolidation due to different reasons. Post transplantation use of TKI remains variable. HyperCVAD and Dasatinib appears to be a reasonable but toxic alternative for patients who are unable to go for allogeneic stem cell transplantation with a reported estimated survival of 64 % at 2 years interval. Disclosures No relevant conflicts of interest to declare.

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Patients with a confirmed NSCLC diagnosis (all stages), aged 18 or above, attending the responsible department of treating this type of disease for the first time at the participating sites from the first of February 2012 to the end of February 2015 were considered eligible. Patients were then informed about the study and were asked to sign an informed consent form which specified that there will be no change in