Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

Cancer is an age‐associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung‐resident γδT cells was significantly increased with altered gene expression in aged mice (20–24 months) versus young mice (10–16 weeks). Aged lung Vγ4⁺ and Vγ6⁺ γδT cells predominantly produced interleukin‐17A (IL‐17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4⁺ and Vγ6⁺ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL‐17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL‐17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co‐housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age‐dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti‐tumor immunotherapy.     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Impact of lung density on isolated lung tumor dose in VMAT using inline MR-Linac

PurposeThis study investigated the impact of lung density on the isolated lung tumor dose for volumetric modulated arc therapy (VMAT) in an inline magnetic resonance linear accelerator (MR-Linac) using the Monte Carlo (MC) simulation.MethodsCT images of the thorax phantoms with lung tumors of 1, 2, and 3 cm diameters were converted into voxel-base phantoms with lung densities of 0.1, 0.2, and 0.3 g/cm³, respectively. The dose distributions were calculated for partial-arc VMAT. The dose distributions were compared using dose differences, dose volume histograms, and dose volume indices.ResultsIn all cases, the inline magnetic field significantly enhanced the lung tumor dose compared to that at 0 T. For the 1 cm lung tumor, the inline magnetic field of 1 T increased the minimum dose of 95% of the Planning target volume (PTV D₉₅) by 14.0% in 0.1 g/cm³ lung density as compared to that in 0.3 g/cm³ at 0 T. In contrast, at 0 and 0.5 T, the PTV D₉₅ in 0.3 g/cm³ lung density was larger than that in lung density of 0.1 g/cm³. For the 2 cm lung tumor, a similar tendency to 1 cm was observed, whereas the dose impact of lung density was smaller than that for 1 cm. For the 3 cm lung tumor, the lung tumor dose was independent of lung density at 0.5 T and 1.0 T.ConclusionThe inline MR-Linac with the magnetic field over 1 T can enhance the PTV D₉₅ for VMAT regardless of the lung density.     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

Circular RNA hsa_circ_0085131 is involved in cisplatin‐resistance of non‐small‐cell lung cancer cells by regulating autophagy

Non‐small‐cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we reported the role of hsa_circ_0085131 in NSCLC. In the present study, NSCLC tumor specimens exhibited a higher hsa_circ_0085131 level in comparison to para‐tumor samples. And the higher level of hsa_circ_0085131 was associated with recurrence and poorer survival of NSCLC. Moreover, hsa_circ_0085131 promoted cell proliferation and cisplatin (DDP)‐resistance. Furthermore, hsa_circ_0085131 regulated cell DDP‐resistance by modulating autophagy. Hsa_circ_0085131 acted as a competing endogenous RNA of miR‐654‐5p to release autophagy‐associated factor ATG7 expression, thereby promoting cell chemoresistance. In conclusion, hsa_circ_0085131 enhances DDP‐resistance of NSCLC cells through sequestering miR‐654‐5p to upregulate ATG7, leading to cell autophagy. Therefore, these findings advocate targeting the hsa_circ_0085131/miR‐654‐5p/ATG7 axis as a potential therapeutic option for patients with NSCLC who are resistant to DDP.     

New insights into small‐cell lung cancer development and therapy

Small‐cell lung cancer (SCLC) accounts for approximately 15% of lung cancer cases; however, it is characterized by easy relapse and low survival rate, leading to one of the most intractable diseases in clinical practice. Despite decades of basic and clinical research, little progress has been made in the management of SCLC. The current standard first‐line regimens of SCLC still remain to be cisplatin or carboplatin combined with etoposide, and the adverse events of chemotherapy are by no means negligible. Besides, the immunotherapy on SCLC is still in an early stage and novel studies are urgently needed. In this review, we describe SCLC development and current therapy, aiming at providing useful advices on basic research and clinical strategy.     

The efficacy of 18F-FDG PET/CT-based diagnostic model in the diagnosis of colorectal cancer regional lymph node metastasis

In order to assess the efficacy of ¹⁸F-FDG PET/CT-based diagnostic model in diagnosing colorectal cancer (CRC) lymph node metastasis (LNM), the ¹⁸F-FDG PET/CT medical records of CRC patients were acquired, and the CRC regional LNM diagnostic model was constructed through the combination of image and grain factors of ¹⁸F-FDG PET/CT. The specific analysis methods include univariate analysis, multivariate analysis, ROC curve analysis, and statistical analysis. The research results showed statistical differences in TNM staging, intestinal obstructions, tumor infiltration, regional lymph node (LN) SUVmax, regional LN minimum dimension, and remote metastasis between the CRC patients in the LNM positive group and the LNM negative group. Through the comparisons between the diagnostic model proposed in the research and other diagnostic methods, it was found that the AUC (95%CI) and sensitivity of the proposed diagnostic model were the highest, the comprehensive diagnostic efficacy of the diagnostic model was optimal. Therefore, it was concluded that the diagnostic model was of significant application values, which provided the basis for subsequent clinical diagnosis of CRC.