Adoptive cell therapy (ACT) has been demonstrated to be one of the most promising cancer immunotherapy strategies due to its active antitumor capabilities in vivo. Engineering T cells to overexpress chimeric antigen receptors (CARs), for example, has shown potent efficacy in the therapy of some hematologic malignancies. However, the efficacy of chimeric antigen receptor T cell (CAR-T) therapy against solid tumors is still limited due to the immunosuppressive tumor microenvironment (TME) of solid tumors, difficulty in infiltrating tumor sites, lack of tumor-specific antigens, antigen escape, and severe side effects. In contrast, macrophages expressing CARs (CAR-macrophages) have emerged as another promising candidate in immunotherapy, particularly for solid tumors. Now at its nascent stage (with only one clinical trial progressing), CAR-macrophage still shows inspiring potential advantages over CAR-T in treating solid tumors, including more abundant antitumor mechanisms and better infiltration into tumors. In this review, we discuss the relationships and differences between CAR-T and CAR-macrophage therapies in terms of their CAR structures, antitumor mechanisms, challenges faced in treating solid tumors, and insights gleaned from clinical trials and practice for solid tumors. We especially highlight the potential advantages of CAR-macrophage therapy over CAR-T for solid tumors. Understanding these relationships and differences provides new insight into possible optimization strategies of both these two therapies in solid tumor treatment.

Background: Our previous studies of human breast and prostate cancer have shown that aberrant immune cell infiltration is associated with focal tumor capsule disruption and tumor cell budding that facilitate invasion and metastasis. Our current study attempted to determine whether aberrant immune cell infiltration would have similar impact on colorectal cancer (CRC).

Objective. To investigate the association of the plasma level of cytokines and blood routine indexes with clinical characteristics in patients with cancer. Methods. We analyzed plasma samples derived from 134 cancer patients. Interleukins (IL) 1β, 2, 4, 5, 6, 8, 10, 12p70, 17, IFN-γ, IFN-α, and TNF-α, and blood routine indexes were measured. The associations of the levels of cytokine and blood routine indexes with demographic and clinical characteristics of cancer patients were analyzed. Partial least-squares discriminant analysis was employed to identify cancer metastasis using these plasma cytokine metrics as input. We compared the predictive effectiveness of numeric machine learning algorithms using these indexes and showed a promising model implemented with random forest. Results. Plasma levels of IL-6 and IL-8 in cancer patients with metastases were higher than those without metastases ( ). Cancer patients without metastases had significantly higher levels of plasma IL-12p70 and percentage of lymphocytes as compared with those with metastases ( ). Our random forest model showed the highest prediction performance (upper quantile AUC, 0.885) among the six machine learning algorithms we evaluated. Conclusion. Our findings suggest that plasma levels of IL-6, IL-8, and IL-12p70 and the percentage of lymphocytes could predict the recurrence, metastasis, and progression of cancer. Our findings will provide guidance for tumor monitoring and treatment.

Chronic neutrophilic leukemia (CNL) is a well-recognized, extremely rare myeloproliferative neoplasm (MPN) with only ~200 reported cases until 2017. The current WHO diagnostic criteria include leukocytosis of ≥ 25 x 109/L with ≥ 80% neutrophils/bands, < 10% circulating neutrophil precursors and <1% blasts (<5% bone marrow blasts). Exclusion criteria includes dysplasia, or clinical/molecular diagnosis of other MPN. The WHO classification was updated in 2016 to include CSF3R T618I and other activating mutations in CSF3R as diagnostic. SETBP1 and ASXL1 mutations are frequent but unspecific in CNL and appear to be of prognostic significance. Hepatosplenomegaly and a hypercellular bone marrow with marked granulocytic hyperplasia are common in CNL, but thrombocytosis has not been reported previously. We report a 72-year-old man with past medical history of hypertension and hepatitis C status post-treatment, who presented with WBC 38.4k/cmm, Hgb 6.3g/dl, MCV 102 fl and platelet count of 2601k/cmm. Reactive etiology of thrombocytosis was ruled out. Peripheral blood smear revealed rare blasts. Bone marrow biopsy was hypercellular (60-80%) with M:E ratio of 10:1, granulocytic and megakaryocytic hyperplasia, clustering of dyspoietic megakaryocytes, no erythroid or myeloid dysplasia and minimal patchy reticulin fibrosis suggestive of primary MPN. Chromosome analysis showed normal karyotype of 46 XY. Molecular studies were negative for BCR-ABL, JAK-2 V617F, CALR and MPL, Next Generation Sequencing revealed mutations in the CSF3R gene (Q781* and T618I) and concurrent inactivating ASXL1-G646fs*12 and activating U2AF1-Q157P mutations. These findings were compatible with a diagnosis of CNL. We describe an unusual case of CNL confirmed by CSF3R gene mutations (T618I and Q781*) with significant thrombocytosis and without splenomegaly. Although the T618I mutation has commonly been reported in CNL, to the best of our knowledge, the Q781* mutation is novel in CNL, and has only been reported before in severe congenital neutropenia (SCN). Association of Q781* mutation in CSF3R gene with significant thrombocytosis in our patient needs further investigation. Disclosures No relevant conflicts of interest to declare.

Background Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment. Methods 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm. Results We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P = 0.00018 and P = 0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion. Conclusions We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.