Myeloid-derived suppressor cells (MDSCs) represent heterogeneous immunosuppressive cells in multiple cancer types and display potent immunosuppressive activity on T cells. We have shown the increased expression of IDO in breast cancer. Because IDO plays a pivotal role in immune tolerance via suppressing T cell function, the aim of this study was to investigate the expression of IDO in MDSCs in breast cancer and its role in MDSC-mediated inhibition of immune surveillance. The proportion of MDSCs with the phenotype of CD45+CD13+CD33+CD14−CD15− significantly increased in primary cancer tissues and patients’ peripheral blood. IDO expression was significantly upregulated in MDSCs isolated from fresh breast cancer tissues (fresh MDSCs [fMDSCs]), which correlated with increased infiltration of Foxp3+ regulatory T cells in tumors and lymph node metastasis in patients. fMDSCs inhibited IL-2 and anti-CD3/CD28 mAb-induced T cell amplification and Th1 polarization but stimulated apoptosis in T cells in an IDO-dependent manner. CD33+ progenitors isolated from healthy donors’ umbilical cord blood were cocultured with breast cancer cell line MDA-MB-231 cells to induce MDSCs. IDO expression was upregulated in induced MDSCs, which required phosphorylation of STAT3, but not STAT1. IDO was required for induced MDSCs’ immunosuppressive activity on T cells, which was blocked by IDO inhibitor 1-methyl-L-tryptophan or STAT3 antagonist JSI-124. Consistently, increased STAT3 phosphorylation level was found in fMDSCs. Together, our findings suggest that STAT3-dependent IDO expression mediates immunosuppressive effects of MDSCs in breast cancer. Thus, inhibition of MDSC-induced T cell suppression by blocking IDO may represent a previously unrecognized mechanism underlying immunotherapy for breast cancer.

Background: Programmed death-1 (PD-1) blocking antibodies have been shown to improve progression-free survival (PFS) and overall survival in a subset of patients with non-small cell lung cancer (NSCLC). However, the objective response rate with these agents remains low, and the vast majority of NSCLC patients require alternative combination treatment regimens to prolong their survival. The purpose of this study was to evaluate the clinical efficacy of autologous cytokine-induced killer (CIK) cell infusions combined with PD-1 blocking antibodies in patients with NSCLC. Methods: In this preliminary study, we investigated the safety and immune function effectiveness of PD-1 blockade antibodies pembrolizumab or nivolumab administered in combination with or without autologous CIK cell infusions in 18 patients with advanced NSCLC. The peripheral blood mononuclear cells were isolated from these patients and the expression level of some cell surface molecules like PD-1 were detected using flow cytometry to reflect the effectiveness of this combination regimen. Results: No treatment-related deaths occurred in either cohort. In comparison with the pretreatment level, CD3 + CD56 + CD16 + T cells were significantly increased with the combination therapy, while myeloid-derived suppressor cells were significantly increased with PD-1 blocking antibody therapy alone but not with combination therapy. Although the serum interleukin-4 level was downregulated following treatment with the combination regimen, interferon-γ levels were unchanged. Conclusions: The purpose of this clinical study was to report the clinical efficacy and lack of exacerbated autoimmune adverse events with a combination of PD-1 blockade and CIK cell infusions in patients with advanced NSCLC, further supporting assessments of this combination in future clinical trials.

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Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC) characterized by poor differentiated, highly invasive, and early systemic metastases, accounts for only 0.4% of all pulmonary malignancies. The overall prognosis is worse than other subtypes of NSCLC. 1 The rapid development of molecular detection and deep understanding of tumor (U.S. vs. U.K spelling) biology highlight the important role of targeted drugs in NSCLC. Some patients with NSCLC harboring specific driver mutations could benefit from targeted therapies. 2,3 Until now, due to its rarity, high aggressiveness, and difficulty in diagnosis, no large-scale prospective studies of PSC are available. Thus, the efficacy of some targeted options in the treatment of PSC is not clear. We report here a novel PSC case, with mutation of

Objective: Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs. Methods: From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests. Results: At the onset of AEs in the irAE group, ferritin (normal range, 35-150 µg/L) rose to a median of 927 µg/L (range, 117-17,825 µg/L) from 86 µg/L at baseline (range, 29-421 µg/L) (P < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 µg/L; range, 32-478 µg/L) (P < 0.001) and the AE group (median, 103 µg/L; range, 23-712 µg/L) (P < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died. Conclusions: Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.

Objective:To retrospectively analyze the clinicopathological characteristics of thyroid cancer patients with respect to age, gender, benign lesions, and lymph node metastasis and to explore the clinicopathological features of multifocal and unifocal papillary thyroid carcinoma with cervical lymph node metastasis. Methods:The clinicopathological data of 14,431 patients with thyroid cancer who underwent surgical treatment for the first time in the Department of Head and Neck Oncology of our hospital from January 2011 to December 2015 were collected, analyzed, and compared in terms of age, gender, pathological type, benign lesions, and lymph node metastasis.Results: Among 14431cases, here were 3259 males and 11172 females, with a male-to-female ratio of 1:3.43. Patients aged 30-59 years accounted for 82.15%. The number of thyroid cancer cases showed an increasing trend year by year (P < 0.001), and papillary carcinoma was the most common (98.47%). Among 14,210 patients with papillary thyroid carcinoma, 4736 cases were in the multi-focus group and 9474 cases were in the single-focus group. Comparison of the pathological characteristics between the two groups showed that the multi-focus group had a higher probability of lymph node metastasis (P < 0.001). A single-focus combination of papillary thyroid carcinoma with benign lesions was more common (P < 0.001), and the difference was statistically significant. Among the cases of multifocal papillary thyroid carcinoma, there were 2812 cases in the multifocal papillary thyroid carcinoma group, and 1924 cases in the unilateral and/or isthmus group. The analysis showed that there were more males, younger patients, more patients with benign lesions, and a higher incidence of unilateral microcarcinoma in the unilateral and/or isthmus multifocal thyroid carcinoma group (P = 0.017). p < 0.001, p < 0.001, and p < 0.001, respectively). There were more patients with cervical lymph node metastasis in the bilateral multifocus group (p = 0.016), and the difference was statistically significant.

Pulmonary sarcomatoid carcinoma; non-small cell lung cancer; EGFR mutation; MET amplification; crizotinib/gefitinib

Background: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with unique features at histological and molecular levels. The prevalence of OCCC is higher in east Asia than in Western countries.As cases are usually chemo-resistant, treatment effects of platinum-based chemotherapy are not satisfactory, especially for patients with stage III or IV disease. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with advanced-stage cancers. However, whether advanced OCCC patients benefit from ICIs remains elusive.Case Presentation: Herein, we report a Chinese patient with stage IIIB inoperable OCCC who was resistant to platinum-based chemotherapy and anlotinib. Next-generation sequencing (NGS) revealed a pathogenic polymerase epsilon (POLE) P286R mutation and a high level of tumor mutation burden (TMB) in tissue and plasma samples. The ICI sintilimab was then used with bevacizumab as third-line treatment.Tumor reduction was observed, and the patient underwent surgical resection which indicated a pathologic complete response (pCR). Maintenance therapy with sintilimab and bevacizumab was applied, and the patient has achieved overall survival (OS) of 35 months since the diagnosis. They have also achieved a progressionfree survival (PFS) of 29 months since commencing ICI treatment and have been disease-free for 24 months after surgical resection. Conclusions:The treatment effect of ICI in POLE-mutant OCCC patients has been rarely reported.The treatment benefits observed in the stage IIIB OCCC patient who was resistant to platinumbased chemotherapy may be associated with the presence of POLE mutation and a high level of TMB.Comprehensive genomic profiling could contribute to appropriate treatment decisions for OCCC.