bims-netuvo 2022-07-17 papers

Issue of 2022‒07‒17
two papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Cancer Immunol Res. 2022 Jul 14. pii: cir.22.0110. [Epub ahead of print]

Sensory nerves impede the formation of tertiary lymphoid structures and development of protective anti-melanoma immune responses.

Kavita Vats, Oleg Kruglov, Bikram Sahoo, Vishal Soman, Jiying Zhang, Galina V Shurin, Uma R Chandran, Pavel Skums, Michael R Shurin, Alex Zelikovsky, Walter J Storkus, Yuri L Bunimovich.

Peripheral neurons comprise a critical component of the tumor microenvironment (TME). The role of the autonomic innervation in cancer has been firmly established. However, the effect of the afferent (sensory) neurons on tumor progression remains unclear. Utilizing surgical and chemical skin sensory denervation methods, we showed that afferent neurons supported the growth of melanoma tumors in vivo and demonstrated that sensory innervation limited the activation of effective anti-tumor immune responses. Specifically, sensory ablation led to improved leukocyte recruitment into tumors, with decreased presence of lymphoid and myeloid immunosuppressive cells and increased activation of T-effector cells within the TME. Cutaneous sensory nerves hindered maturation of intratumoral high endothelial venules (HEVs) and limited formation of mature tertiary lymphoid-like structures containing organized clusters of CD4+ T cells and B cells. Denervation further increased T-cell clonality and expanded the B-cell repertoire in the TME. Importantly, CD8a depletion prevented denervation-dependent anti-tumor effects. Finally, we observed that gene signatures of inflammation and the content of neuron-associated transcripts inversely correlated in human primary cutaneous melanomas, with the latter representing a negative prognostic marker of patient overall survival. Our results suggest that tumor-associated sensory neurons negatively regulate the development of protective anti-tumor immune responses within the TME, thereby defining a novel target for therapeutic intervention in the melanoma setting.

DOI: https://doi.org/10.1158/2326-6066.CIR-22-0110

Eur J Surg Oncol. 2022 Jun 25. pii: S0748-7983(22)00536-4. [Epub ahead of print]

Prognostic role of perineural invasion in vulvar squamous cell carcinoma: A systematic review and meta-analysis.

Angela Santoro, Giuseppe Angelico, Antonio Travaglino, Frediano Inzani, Damiano Arciuolo, Michele Valente, Nicoletta D'Alessandris, Giulia Scaglione, Alessia Piermattei, Federica Cianfrini, Patrizia Straccia, Roberta Benvenuto, Antonio Raffone, Giorgia Garganese, Valerio Gallotta, Gian Franco Zannoni.

The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p < 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

Keywords: Perineural invasion; Prognosis; Risk factor; Squamous cell carcinoma; Vulvar cancer

DOI: https://doi.org/10.1016/j.ejso.2022.06.031