Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small cell lung cancer

immuneACCESS ◽  
2019 ◽  
Author(s):  
Y Kudo ◽  
C Haymaker ◽  
J Zhang ◽  
A Reuben ◽  
DY Duose ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Lumeng Luo ◽  
Peiyi Liu ◽  
Kuaile Zhao ◽  
Weixin Zhao ◽  
Xiaofei Zhang

Brain metastasis of non-small cell lung cancer is associated with poor survival outcomes and poses rough clinical challenges. At the era of immunotherapy, it is urgent to perform a comprehensive study uncovering the specific immune microenvironment of brain metastases of NSCLC. The immune microenvironment of brain is distinctly different from microenvironments of extracranial lesions. In this review, we summarized the process of brain metastases across the barrier and revealed that brain is not completely immune-privileged. We comprehensively described the specific components of immune microenvironment for brain metastases such as central nervous system-derived antigen-presenting cells, microglia and astrocytes. Besides, the difference of immune microenvironment between brain metastases and primary foci of lung was particularly demonstrated.


2019 ◽  
Vol 30 (9) ◽  
pp. 1521-1530 ◽  
Author(s):  
Y. Kudo ◽  
C. Haymaker ◽  
J. Zhang ◽  
A. Reuben ◽  
D.Y. Duose ◽  
...  

2021 ◽  
Vol 16 (4) ◽  
pp. S714-S715
Author(s):  
S. Rakshit ◽  
R. Bansal ◽  
A. Desai ◽  
K. Leventakos

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1562
Author(s):  
Konstantinos Rounis ◽  
Marcus Skribek ◽  
Dimitrios Makrakis ◽  
Luigi De Petris ◽  
Sofia Agelaki ◽  
...  

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2141
Author(s):  
Paola Anna Jablonska ◽  
Joaquim Bosch-Barrera ◽  
Diego Serrano ◽  
Manuel Valiente ◽  
Alfonso Calvo ◽  
...  

Approximately 20% patients with non-small cell lung cancer (NSCLC) present with CNS spread at the time of diagnosis and 25–50% are found to have brain metastases (BMs) during the course of the disease. The improvement in the diagnostic tools and screening, as well as the use of new systemic therapies have contributed to a more precise diagnosis and prolonged survival of lung cancer patients with more time for BMs development. In the past, most of the systemic therapies failed intracranially because of the inability to effectively cross the blood brain barrier. Some of the new targeted therapies, especially the group of tyrosine kinase inhibitors (TKIs) have shown durable CNS response. However, the use of ionizing radiation remains vital in the management of metastatic brain disease. Although a decrease in CNS-related deaths has been achieved over the past decade, many challenges arise from the need of multiple and repeated brain radiation treatments, which carry along not insignificant risks and toxicity. The combination of stereotactic radiotherapy and systemic treatments in terms of effectiveness and adverse effects, such as radionecrosis, remains a subject of ongoing investigation. This review discusses the challenges of the use of radiation therapy in NSCLC BMs in view of different systemic treatments such as chemotherapy, TKIs and immunotherapy. It also outlines the future perspectives and strategies for personalized BMs management.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sebastian Johannes Müller ◽  
Eya Khadhraoui ◽  
Nicole E. Neef ◽  
Christian Heiner Riedel ◽  
Marielle Ernst

Abstract Background Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less  aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC. Methods We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere. Results Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988. Conclusions In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer. Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).


Sign in / Sign up

Export Citation Format

Share Document