The Immune Landscape of Human Primary Lung Tumors Is Th2 Skewed

Tumor-specific T helper (Th) cells have a central role in the immune response against cancer. However, there exist distinct Th cell subsets with very different and antagonizing properties. Some Th subsets such as Th1 protect against cancer, while others (Th2, T regulatory/Treg) are considered detrimental or of unknown significance (T follicular helper/Tfh, Th17). The Th composition of human solid tumors remains poorly characterized. Therefore, we established a four-color multiplex chromogenic immunohistochemical assay for detection of Th1, Th2, Th17, Tfh and Treg cells in human tumor sections. The method was used to analyze resected primary lung tumors from 11 patients with non-small cell lung cancer (NSCLC). Four microanatomical regions were investigated: tumor epithelium, tumor stroma, peritumoral tertiary lymphoid structures (TLS) and non-cancerous distal lung tissue. In tumor epithelium and stroma, most CD4+ T cells identified had either a Th2 (GATA-3+CD3+CD8-) or Treg (FOXP3+CD3+CD8-) phenotype, whereas only low numbers of Th1, Th17, and Tfh cells were observed. Similarly, Th2 was the most abundant Th subset in TLS, followed by Treg cells. In sharp contrast, Th1 was the most frequently detected Th subset in non-cancerous lung tissue from the same patients. A higher Th1:Th2 ratio in tumor stroma was found to be associated with increased numbers of intratumoral CD8+ T cells. The predominance of Th2 and Treg cells in both tumor stroma and tumor epithelium was consistent for all the 11 patients investigated. We conclude that human primary NSCLC tumors are Th2-skewed and contain numerous Treg cells. If human tumors are Th2-skewed, as our data in NSCLC suggest, reprogramming the type of immune response from a detrimental Th2 to a beneficial Th1 may be critical to increase the response rate of immunotherapy.

Correlation between Imaging Features and Pathological Stages of Primary Lung Tumors Based on Nanocontrast Agents

As one of the conventional methods of lung cancer detection, computed tomography (CT) usually requires the use of contrast agents to enhance the imaging effect. Conventional iodine contrast agents have poor signal-to-noise ratio and are prone to adverse reactions. It is necessary to find more effective and safe contrast agents for CT scans. The gold nanoparticles with secondary electron effect and photoelectric absorption effect can prolong the display time of the patient’s blood circulation after being injected into the patient’s body, which makes the nanocontrast agent a research hotspot in the field of CT imaging. In this study, ultrasmall gold nanoclusters with a diameter of about 5 nm were used as the contrast agent in CT scans. It was found that CT scans based on nanocontrast agents can obtain high-quality lung cancer imaging images, and the patient has no obvious adverse reactions. When observing the CT image, it was found that the stage of lung cancer patients can be clearly distinguished through the CT scan image. When analyzing the consistency of CT imaging and pathological classification, the Kappa value was 0.810, indicating that the two have a high degree of consistency. Therefore, this study believes that the imaging characteristics of primary lung tumors based on nanocontrast agents are highly correlated with their pathological types.

CT Evaluation of Unilateral Destroyed Lung among Bangladeshi Population

The unilateral destroyed lung is an important cause of morbidity and mortality. The commonest cause of destroyed lung is total post tuberculous sequelae. Primary lung tumors, mediastinal masses, vascular abnormalities, and some others are considered to be other causes of lung destruction. A study was undertaken at the National Institute of Diseases of the Chest and Hospital (NIDCH) on 600 cases from January 2016 to December 2020 to evaluate the etiopathogenesis of unilateral lung destruction and to evaluate hilar structures & the nature and extent of parenchymal damage. The study was performed on 600 patients with unilateral lung destruction, of whom 416(69.33%) had left lung destruction. Pulmonary tuberculosis was found to be the cause in 504(84%) patients. All patients had an X-ray chest and CT scan of the chest (contrast CT/ HRCT). However, 96(16%) non-tuberculous patients had their main bronchi occluded with extraluminal compression or by the intraluminal lesion. TAJ 2021; 34: No-1: 75-79

Pulmonary metastatic melanoma: current state of diagnostic imaging and treatments

Melanoma is the deadliest form of skin cancer with an estimated incidence of over 160,000 cases annually and about 41,000 melanoma-related deaths per year worldwide. Malignant melanoma (MM) primarily occurs in the skin but has been described in other organs. Although the respiratory system is generally afflicted by tumors such as lung cancer, it is also rarely affected by primary MM. The estimated incidence of pulmonary MM of the lung accounts for 0.01% of all primary lung tumors. The current understanding of pulmonary MM of the lung pathophysiology and its management are not well established. We aim to survey current clinical modalities with a focus on diagnostic imaging and therapeutic intervention to guide providers in the management of patients with a high index of suspicion.

Lung Cancer Management with Silibinin: A Historical and Translational Perspective

The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules.

Comparison of immune microenvironment between primary lung tumors and paired brain metastatic tumors.

2020 Background: Lung cancer is one of the most common causes of brain metastases (BMs) and is always associated with poor prognosis. To evaluate the characteristics of the tumor immune microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and paired brain metastases. Methods: Forty-three Chinese patients with NSCLC who had BMs at presentation or during the course of their disease were admitted to the Sun Yat-Sen University Cancer Center (Guangzhou, China) from 2000 to 2019. RNA sequencing (RNA-seq) of eighty-six formalin-fixed, paraffin embedded (FFPE) samples from primary lung tumors and paired brain metastases of 43 patients was conducted to comprehensively analyze the tumor immune microenvironment. Results: Our data revealed that brain metastases compared with primary lung tumors exhibited reduced tumor infiltrating lymphocytes (TILs) (all 28 immune cell subtypes P < 0.05), lower fraction of activated CD8 T cell and effector memory CD8 T cell in total TILs (P = 0.028, P < 0.001, respectively); higher fraction of macrophage and neutrophil in total TILs (P < 0.001, P < 0.01, respectively). Comparing with the primary lung tumors, the scores of some immune related signatures, including MHC non-class signature, IFN gamma signature and T-cell-inflamed gene-expression profile (GEP) signature, were significantly lower in brain metastases (P = 0.004, P = 0.009, P = 0.004, respectively), while the score of MHC class-II signature was higher in brain metastases (P = 0.045). We found the distributions of tumor microenvironment immune types (TMIT) in brain metastases and primary lung tumors were different. Brain metastases contained significantly lower proportion of TMIT I (high PD-L1/ high CD8A) (23%) than primary lung tumors (47%) (P < 0.05). Besides, we found three immune inhibitory checkpoint molecules, namely C10orf54 (VISTA), CTLA4 and CD274 (PD-L1) were downregulated in brain metastases than in primary lung tumors (P < 0.001, P < 0.001, P = 0.034, respectively). Moreover, there was poor correlation of PD-L1 expression between paired brain metastases and primary lung tumors (R = 0.28, P = 0.068). Unsupervised hierarchic cluster analysis revealed the primary lung tumors had two distinct patterns of immune gene signatures, namely Cluster A and Cluster B, and the tumors in Cluster B were immune rich, but associated with poor prognosis (log-rank P = 0.021). Conclusions: Our work illustrates the immune landscape of brain metastases from NSCLC, and suggests that the tumor immune microenvironment in brain metastases compared with primary lung tumors is further immunosuppressed, that may help guide immunotherapeutic strategies for NSCLC brain metastases.

Umwelt-Radongehalt und primäre Lungentumoren bei Hund und Katze

Fowler BL, Johannes CM, O’Connor A et al. Ecological level analysis of primary lung tumors in dogs and cats and environmental radon activity. J Vet Int Med 2020; 34 (6): 2660–2670 Epidemiologische Studien beim Menschen weisen darauf hin, dass zwischen dem häuslichen Radongehalt und der Entwicklung primärer Lungentumoren ein Zusammenhang besteht. In den USA ist eine Radonexposition die geschätzt zweithäufigste Ursache dieser Tumorerkrankung. Aufgrund einer Vielzahl von Einflussfaktoren lässt sich ein kausaler Zusammenhang jedoch nur schwer nachweisen. In der Veterinäronkologie liegen bisher keine Daten hierzu vor. Ziel dieser Studie war daher, die Inzidenz primärer Lungentumoren bei Hunden und Katzen in Relation zum Radongehalt in der Umwelt zu ermitteln.

Application of large-scale targeted sequencing to distinguish multiple lung primary tumors from intrapulmonary metastases

The effective differentiation between multiple primary lung tumors (MPs) and intrapulmonary metastases (IMs) in patients is imperative to discover the exact disease stage and to select the most appropriate treatment. In this study, the authors was to evaluate the efficacy and validity of large-scale targeted sequencing (LSTS) as a supplement to estimate whether multifocal lung cancers (MLCs) are primary or metastatic. Targeted sequencing of 520 cancer-related oncogenes was performed on 36 distinct tumors from 16 patients with MPs. Pairing analysis was performed to evaluate the somatic mutation pattern of MLCs in each patient. A total of 25 tumor pairs from 16 patients were sequenced, 88% (n = 22) of which were classified as MPs by LSTS, consistent with clinical diagnosis. One tumor pair from a patient with lymph node metastases had highly consistent somatic mutation profiles, thus predicted as a primary-metastatic pair. In addition, some matched mutations were observed in the remaining two paired ground-glass nodules (GGNs) and classified as high-probability IMs by LSTS. Our study revealed that LSTS can potentially facilitate the distinction of MPs from IMs. In addition, our results provide new genomic evidence of the presence of cancer invasion in GGNs, even pure GGNs.