"Brain metastases are a long-known devastating complication of advanced malignancies that lead to substantial morbidity. As patients with metastatic cancer are expected to live longer with newer systemic therapeutic agents and with better and more sensitive imaging studies, it is expected that more patients will be diagnosed with brain metastases. In the past, traditional treatment approaches included surgery or radiation therapy, or a combination of the two. Chemotherapeutic agents were generally used for refractory disease. However, in the last few years, several treatment advances in targeted therapy and immunotherapy have changed the landscape of the management of brain metastases. Recently, the American Society of Clinical Oncology (ASCO) announced cancer immunotherapy as the “advance of the year,”1 and its role in the management of brain metastases is undergoing active investigation. There has been a paucity of research focused on brain metastases; as a result, there are several unanswered questions. In this article, we present the available evidence regarding the interactions between the immune system and brain parenchyma in brain metastases, the clinical application of immune checkpoint inhibitors in the management of brain metastases, and the potential of combining radiation with immune checkpoint inhibitor"
http://meetinglibrary.asco.org/record/5 ... k#fulltext
Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment
Differential Reactions of Microglia to Brain Metastasis of Lung Cancer
Differential Reactions of Microglia to Brain Metastasis of Lung Cancer
Abstract
The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidated. In this study, we have investigated microglial reactions in brain tissues with metastatic lung cancer cells and evaluated the cytotoxic effects of lipopolysaccharide (LPS)-activated microglia on metastatic lung cancer cells in vitro. In the vicinity of metastatic lung cancer mass in the brain, microglia showed signs of significant activation. There was an obvious increase in the number of microglia labeled with ionized calcium binding adaptor molecule 1 (Iba-1) antibody, a specific marker of microglia. The microglia were observed to form a clear boundary between the tumor mass and normal brain tissue. In the region where the tumor mass was situated, only a few microglia expressed inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), indicating differential activation in those microglia. The supernatant from LPS-activated microglia induced apoptosis of metastatic lung cancer cells in vitro in a dose- and time-dependent manner. However, at lower concentrations of activated microglial supernatant, trophic effects on cancer cells were observed, some lung cancer cells being insensitive to microglial cytotoxicity. Together with the observation that TNF-α alone induced proliferation of the tumor cells, the findings provide possible clues to the mechanism involved in metastasis of lung cancer cells to the brain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626596/
Abstract
The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidated. In this study, we have investigated microglial reactions in brain tissues with metastatic lung cancer cells and evaluated the cytotoxic effects of lipopolysaccharide (LPS)-activated microglia on metastatic lung cancer cells in vitro. In the vicinity of metastatic lung cancer mass in the brain, microglia showed signs of significant activation. There was an obvious increase in the number of microglia labeled with ionized calcium binding adaptor molecule 1 (Iba-1) antibody, a specific marker of microglia. The microglia were observed to form a clear boundary between the tumor mass and normal brain tissue. In the region where the tumor mass was situated, only a few microglia expressed inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), indicating differential activation in those microglia. The supernatant from LPS-activated microglia induced apoptosis of metastatic lung cancer cells in vitro in a dose- and time-dependent manner. However, at lower concentrations of activated microglial supernatant, trophic effects on cancer cells were observed, some lung cancer cells being insensitive to microglial cytotoxicity. Together with the observation that TNF-α alone induced proliferation of the tumor cells, the findings provide possible clues to the mechanism involved in metastasis of lung cancer cells to the brain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626596/
Debbie
Re: Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment
Most of the ICI clinical trials exclude patients with the brain metastases...some exclude only untreated but some also any known brain mets. Leaving the patients to try these drugs off label, without the supervision or documenting response/side effects.
Olga
Re: Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment
Olga that was going to be my point today 
With immune therapies being so incredibly new , there are lots of clinical trials going on pertaining to immune therapies and metastatic brain cancers.
I felt it important to post the write up as we have had Opdivo resolve a skull met that was 9mm and 1- 3mm lower tumor in Joshua's brain disappear as well.
I'll locate the clinical trials I had read of and post them
From first write up
From the 2016 ASCO conference
Need to go to table 2-
"Another multicenter phase II clinical trial of ipilimumab plus nivolumab for patients with advanced melanoma with brain metastases (NCT02320058) is currently accruing patients.39 This study is planned to treat patients with asymptomatic brain metastases from melanoma with an induction phase of four cycles of 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks, followed by maintenance therapy of 3 mg/kg of nivolumab every 2 weeks. Table 2 provides a list of other important clinical trials in this setting."
http://meetinglibrary.asco.org/record/5 ... k#fulltext
With immune therapies being so incredibly new , there are lots of clinical trials going on pertaining to immune therapies and metastatic brain cancers.
I felt it important to post the write up as we have had Opdivo resolve a skull met that was 9mm and 1- 3mm lower tumor in Joshua's brain disappear as well.
I'll locate the clinical trials I had read of and post them
From first write up
From the 2016 ASCO conference
Need to go to table 2-
"Another multicenter phase II clinical trial of ipilimumab plus nivolumab for patients with advanced melanoma with brain metastases (NCT02320058) is currently accruing patients.39 This study is planned to treat patients with asymptomatic brain metastases from melanoma with an induction phase of four cycles of 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks, followed by maintenance therapy of 3 mg/kg of nivolumab every 2 weeks. Table 2 provides a list of other important clinical trials in this setting."
http://meetinglibrary.asco.org/record/5 ... k#fulltext
Debbie