BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.

Killer‐cell immunoglobulin‐like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south‐western Iran. KIR genes and KIR2DS4 variants were typed by polymerase chain reaction–sequence‐specific primer (PCR‐SSP) in 167 patients with AML and 169 healthy controls. Our results showed 10% of patients—mostly females—were classified as M3. Flt3 mutations were detected in 26% of patients, most of whom had internal tandem duplication (ITD). The frequency of activating KIRs (aKIRs)—mainly KIR3DS1—was higher in patients, whereas inhibitory KIRs (iKIRs)—particularly KIR3DL1 and KIR2DL1—were more common among controls. The incidence of the KIR2DS4fl allele was higher among patients with non‐M3 AML than controls. We also found a higher frequency of 4 or more iKIR genes in the controls and a higher frequency of 4 or more aKIR genes in the patients. Individuals with more iKIR than aKIR belonged predominantly to the control group. Individuals with the telomeric AA genotype who had inherited the KIR2DS4fl allele were more frequent in the patient group. According to our results, increased frequency of aKIRs in patients with AML may lead to the hyperactivation of NK cells against malignant cells with reduced or lack of HLA class I molecules followed by NK cell exhaustion which allow malignant cells to progress.

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Radioactive iodine (RAI)-induced thyrocyte destruction may lead to uncontrolled inflammation. This study was designed to evaluate the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer scheduled for RAI ablation. A total of 85 patients were divided into two groups based on radioiodine dosage after thyroidectomy: high-dose with 150 mCi and intermediate-dose with 100 mCi. Then patients in each group were randomly divided into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Serum cytokine levels were determined with the cytometric bead assay at different time points. Within-group comparisons showed transient elevation of IL-13 after pretreatment with omega-3, significant reductions in Th1+Th17/Th2+Th22 ratio after high-dose RAI ablation, and decreased Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios after intermediate-dose RAI ablation in G2. Between-group comparisons showed that IL-10 level in G3 was significantly higher than in G1 1 week after high-dose RAI ablation, whereas Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were significantly lower in G3 than G2 1 month after intermediate-dose RAI ablation. However, cytokine changes 1 week and 1 month after RAI ablation when adjusted for baseline values showed no differences among groups. Despite observing within-group changes in some cytokines, we found no real changes attributable to a prophylactic or therapeutic anti-inflammatory effect of omega-3. Because of the specific effect of radioactive iodine on thyroid cells, extensive systemic inflammation may not be induced after RAI ablation.

Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.