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Abstract Background We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. Results The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. Conclusion Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

Purpose: Family with sequence similarity 83 member H (FAM83H) plays key roles in tumorigenesis. However, the specific roles of FAM83H in cervical cancer (CC) have not been well studied. Materials and Methods: The RNA-seq data of 306 CC tissues and three normal samples downloaded from The Cancer Genome Atlas were used to analyze the expression of FAM83H. The Kaplan-Meier method was used to draw survival curves. Associations between FAM83H expression and clinicopathological factors were analyzed by chi-square test. Cox proportional hazards model was used to analyze prognostic factors. Loss-of-function assays were conducted to discover the biological functions of FAM83H in cell proliferation, colony formation, invasion, and migration. Real-time Quantitative Reverse Transcription PCR (qRT-PCR) and Western blotting were used to measure the expression levels of FAM83H in CC cell lines. Results: Our results demonstrated that FAM83H is overexpressed in CC tissues and that high FAM83H expression is associated with worse overall survival (OS). High FAM83H expression in CC was associated with clinical stage, pathologic tumor, and pathologic node. Univariate analysis suggested that FAM83H expression was significantly related to the OS of CC patients. Although multivariate analysis showed that FAM83H expression was not an independent prognostic factor for the OS of CC patients, the effects of FAM83H on CC cell growth and motility was significant. Loss-of-function experiments demonstrated that knockdown of FAM83H inhibited proliferation, colony formation, migration, and invasion of CC cells by inactivating PI3K/AKT pathway. Conclusion: FAM83H might play a crucial role in CC progression and could act as a novel therapeutic target in CC. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma with a micropapillary pattern (MPPAC) has recently drawn increased attention among researchers. Micropapillary-predominant adenocarcinoma (MPA), which is defined by micropapillary pattern (MPP), is the primary histological pattern observed semiquantitatively in 5% increments on resection specimens, and MPA was formally determined to be a new histological subtype according to the new multidisciplinary classification in 2011. According to published studies, MPPAC is most common in males and nonsmokers and is associated with lymphatic invasion, pleural invasion, and lymph node metastases. MPPAC often presents as part-solid and lobulated nodules in computed tomography scans. MPP tends to have a higher maximum standardized uptake value as determined by fluorodeoxyglucose positron emission tomography combined with computed tomography, indicating a high risk of recurrence. Molecular markers, including vimentin, napsin A, phosphorylated c-Met, cytoplasmic maspin, Notch-1, MUC1, and tumoral CD10, may have higher expression in MPPAC than other subtypes; conversely, markers such as MUC4 and surfactant apoprotein A have lower expression in MPPAC. MPPAC with EGFR mutations can benefit from treatment with EGFR tyrosine kinase inhibitors. Furthermore, a complete lobectomy may be more suitable than limited resection for MPPAC because of the low sensitivity of intraoperative frozen sections and the high risk of lymph node metastasis. MPA benefits more from adjuvant chemotherapy than do other histological subtypes, whereas MPA does not benefit from adjuvant radiotherapy. Of note, MPP is associated with poor prognosis in early-stage lung adenocarcinoma, but the prognostic value of MPP is controversial in advanced-stage lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.