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  1. Unanswered Questions - Stack Overflow
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  3. 2. Have I done everything in my power?

FOXP3, among other functions, is responsible for the differentiation of Tregs and the maintenance of their signaling. Pentoxifylline is an FDA-approved drug, already in the market, used in patients to increase blood flow in the hands and feet of people with poor circulation.

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It also causes c-Rel degradation and impairs Treg identity Of course, caution should be taken since the destruction of Tregs can generate autoimmune reactions. Immunotherapy in lung cancer has demonstrated significant activity in early stage disease In addition, he said that the study prompts us to gain further insights on the immune effects of irradiation Whether the effect of immunotherapy can be stronger in the neoadjuvant setting compared to after dissection of lymph nodes, which can reduce the anti-tumor activity of the immune system, merits further investigation in lung cancer 56 , In breast cancer mice models, neoadjuvant immunotherapy had a significant better therapeutic efficacy in comparison with adjuvant therapy The rapid proliferation and differentiation of T cells is necessary for an effective PD-1 blockade therapy.

Immune metabolism requires mitochondria in draining lymph nodes to supply tumor-reactive cytotoxic T lymphocytes with ATP, but the preexisting cytotoxic T lymphocytes are not enough for durable tumor-growth inhibition. Indeed, draining lymph node ablation cancels the efficacy of the PD-1 blockade therapy Immunotherapy constitutes a milestone in the advancement of lung cancer treatment.

We report the case of a year-old male patient who arrived to our institution in April , with a metastatic squamous cell carcinoma of the lung and progression to first-line therapy.

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The patient was initially diagnosed in October, , with a squamous cell carcinoma of the lung and brain metastases. He was treated in his local hospital with four cycles of cisplatin with paclitaxel, consolidation radiotherapy of the lung and the mediastinum and radiosurgery of the brain metastases. Only three months after the end of the treatment, he progressed with new liver and bone metastases.

At that time the patient came to us with a performance status of 2 for a second opinion. There was no tissue available for molecular analysis and we planned to perform a biopsy of the liver metastases if the performance status of the patient improved with the treatment.

An impressive clinical, radiographic and metabolic response, with complete disappearance of the liver metastases was observed after only 6 administrations of nivolumab. The patient is still radiographically free of disease after 42 cycles , 2 years and 6 months after being diagnosed with metastatic NSCLC.

We never had the opportunity to perform a rebiopsy. The patient continues therapy with nivolumab without any significant toxicity Figure 3. Immune related toxicities are out of the scope of our review, but there are several reports and guidelines that are useful for oncologists and hospitalists who are treating patients receiving immune checkpoint inhibitors 95 , In the first-line setting of NSCLC patients without driver genetic alterations, treatment decisions have become more complex than in the past.

The results of the CheckMate showed that nivolumab plus ipilimumab is an effective treatment option for patients with high TMB. Still, there are several challenges, such as the reliability of the metrics to identify patients with high TMB or the tissue requirements for such analysis that usually surpasses the quantity of material that we obtain by performing small biopsies. Furthermore, the turnaround time of a targeted next generation sequencing cannot be less than 10 days, the cost of the test is significantly high and it is not easily available in all hospitals.

In the CheckMate, patients were not randomized by TMB and the overall survival results are relatively immature with a non-significant trend toward improved overall survival for patients with high TMB receiving the immunotherapy combination. On the other hand, we have the results of the Keynote in which the benefit in progression-free and overall survival of pembrolizumab combined with platinum-based chemotherapy extended across all PD-L1 levels, even patients with low PD-L1 expression. Last but not least we should not forget that pembrolizumab alone has comparable efficacy to pembrolizumab combined with platinum-based chemotherapy, has lower risks for side-effects and preserves the option of platinum-based chemotherapy upon disease progression, for patients with high PD-L1 Looking at the results of the most relevant clinical trials comparing immunotherapy with chemotherapy 11 , 15 , we observe that survival curves separate at later times Lalala feat.

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2. Have I done everything in my power?

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