bims-netuvo 2023-06-04 papers

Issue of 2023‒06‒04
five papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Clin Oncol (R Coll Radiol). 2023 May 19. pii: S0936-6555(23)00186-3. [Epub ahead of print]

The Incidence and Prognosis Value of Perineural Invasion in Rectal Carcinoma: From Meta-Analyses and Real-World Clinical Pathological Features.

T Chen, B Zheng, P Yang, Z Zhang, Y Su, Y Chen, L Luo, D Luo, Y Lin, R Xie, L Zeng.

AIMS: Perineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking.MATERIALS AND METHODS: First, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated.
RESULTS: The incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer.
CONCLUSION: PNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.

Keywords: Perineural invasion; prognosis; rectal cancer; recurrence and metastasis

DOI: https://doi.org/10.1016/j.clon.2023.05.008

Trends Cancer. 2023 May 30. pii: S2405-8033(23)00085-7. [Epub ahead of print]

Neuro-immune interactions and immuno-oncology.

Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit.

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune circuits in the tumor milieu, while emphasizing the potential targets of new and affordable anticancer therapeutic approaches.

Keywords: cancer; immunology; immunotherapy; neuroimmunology; neuroscience; oncology

DOI: https://doi.org/10.1016/j.trecan.2023.05.002

Mol Pain. 2023 May 31. 17448069231182235

Contribution of immune cells to cancer-related neuropathic pain: An updated review.

He Ma, Zhenxiang Pan, Bingjie Lai, Mingyue Li, Jingping Wang.

Given that the incidence of cancer is dramatically increasing nowadays, cancer-related neuropathic pain including tumor-related and therapy-related pain gradually attracts more attention from researchers, which basically behaves as a metabolic-neuro-immune disorder with worse clinical outcomes and prognosis. Among various mechanisms of neuropathic pain, the common underlying one is the activation of inflammatory responses around the injured or affected nerve(s). Innate and adaptive immune reactions following nerve injury together contribute to the regulation of pain. On the other hand, the tumor immune microenvironment involving immune cells, as exemplified by lymphocytes, macrophages, neutrophils and dendritic cells, inflammatory mediators as well as tumor metastasis have added additional characteristics for studying the initiation and maintenance of cancer-related neuropathic pain. Of interest, these immune cells in tumor microenvironment exert potent functions in promoting neuropathic pain through different signaling pathways. To this end, this review mainly focuses on the contribution of different types of immune cells to cancer-related neuropathic pain, aims to provide a comprehensive summary of how these immune cells derived from the certain tumor microenvironment participate in the pathogenesis of neuropathic pain. Furthermore, the clarification of roles of various immune cells in different tumor immune microenvironments associated with certain cancers under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction, and thereby provides more opportunities for novel approaches for the prevention and treatment of cancer-related neuropathic pain.

Keywords: Neuropathic pain; T cells; cancer; dendritic cells; immune cells; macrophages; neutrophils; tumor immune microenvironment

DOI: https://doi.org/10.1177/17448069231182235

Neuro Oncol. 2023 May 29. pii: noad097. [Epub ahead of print]

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).METHODS: Genomic analysis was performed on all PDX-tumor pairs. Select PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, and mirdametinib) ex vivo and in vivo. For 3D microtissue studies, cell viability was the endpoint as assessed by Zeiss Axio Observer. For PDX drug studies, tumor volume was measured twice weekly. Bulk RNA sequencing was performed to identify pathways enriched in cells.
RESULTS: We developed 13 NF1-associated MPNST-PDX and identified mutations or structural abnormalities in NF1 (100%), SUZ12 (85%), EED (15%), TP53 (15%), CDKN2A (85%) and chromosome 8 gain (77%). We successfully assembled PDX into 3D microtissues, categorized as robust (>90% viability at 48h), good (>50%), or unusable (<50%). We evaluated drug response to "robust" or "good" microtissues, namely MN-2, JH-2-002, JH-2-079-c and WU-225. Drug response ex vivo predicted drug response in vivo, and enhanced drug effects were observed in select models.
CONCLUSIONS: These data support the successful establishment of a novel 3D platform for drug discovery and MPNST biology exploration in a system representative of the human condition.

Keywords: 3D microtissues; NF1-MPNST; PDX; drug screening; genomic variants

DOI: https://doi.org/10.1093/neuonc/noad097

Cureus. 2023 Apr;15(4): e38187

Soft Tissue Tumor Without Neurofibromatosis Type 1 With Histopathological Suspicion of Atypical Neurofibromatous Neoplasm of Uncertain Biological Potential (ANNUBP).

Hiroyuki Tsuchie, Hiroyuki Nagasawa, Hiroshi Nanjyo, Naohisa Miyakoshi.

Atypical neurofibromatous neoplasm of uncertain biological potential (ANNUBP), defined as a borderline lesion that is difficult to distinguish whether benign or malignant, is one of the intermediate stages to malignant peripheral nerve sheath tumor, a peripheral nerve-derived malignant tumor that develops from nerve sheath cells. Because ANNUBP is a new concept, only a few cases have been reported, all in patients with neurofibromatosis type 1 (NF-1).An 88-year-old woman presented with a mass on the left upper arm persisting for one year. Magnetic resonance imaging showed a large tumor spreading between the humerus and biceps muscle, which was diagnosed as undifferentiated pleomorphic sarcoma by needle biopsy. Extensive tumor resection was performed, including partial cortical bone resection of the humerus. Based on the histological features, although the patient did not have NF-1, the tumor was strongly suspected to be ANNUBP. As malignant peripheral nerve sheath tumors have been sporadically reported in patients without NF-1, it is feasible that ANNUBP could also occur in patients without NF-1.

Keywords: atypical neurofibromatous neoplasm; neurofibromatosis type 1; older adult; positron-emission tomography; soft tissue tumor

DOI: https://doi.org/10.7759/cureus.38187