Delayed cytokine release syndrome after neoadjuvant nivolumab: a case report and literature review.

Aim: Cytokine release syndrome (CRS) is an infrequently described immune-related adverse event of checkpoint inhibitors (CPI). CPI-induced CRS typically presents with fevers, hemodynamic instability and organ dysfunction within 2 weeks of the last treatment cycle. Case study: We report an unusual case of delayed and severe CRS occurring postoperatively in a patient with hepatic-limited metastatic colorectal cancer who received neoadjuvant immunotherapy. After a negative workup for alternative causes, he received prolonged corticosteroid treatment with symptom resolution. Conclusion: CPI-induced CRS can mimic sepsis and clinicians should maintain a high-index of suspicion to diagnose this immune-related adverse event early and initiate appropriate treatment. As use of perioperative immunotherapy increases, the potential role of surgery to trigger CRS in this case warrants further investigation.

Lay abstract Aim: Cytokine release syndrome (CRS) is a rare but potentially serious side effect of a class of immunotherapy drugs called checkpoint inhibitors (CPI). CRS typically presents with fevers and low blood pressure and can cause damage to organs including the kidneys and liver. Case study: We report an unusual case of severe CRS occurring after surgery in a patient who had received prior CPI therapy. After a thorough evaluation for alternative causes, he was diagnosed with CRS and treated successfully with steroids. Conclusion: It is important for medical providers to consider this potential side effect when treating patients with CPI. Further research is needed to clarify the role of surgery in CPI-induced CRS.

The unique immune microenvironment of liver metastases: Challenges and opportunities.

Liver metastases from gastrointestinal and non-gastrointestinal malignancies remain a major cause of cancer-related mortality and a major clinical challenge. The liver has unique properties that facilitate metastatic expansion, including a complex immune system that evolved to dampen immunity to neoantigens entering the liver from the gut, through the portal circulation. In this review, we describe the unique microenvironment encountered by cancer cells in the liver, focusing on elements of the innate and adaptive immune response that can act as a double-edge sword, contributing to the elimination of cancer cells on the one hand and promoting their survival and growth, on the other. We discuss this microenvironment in a clinical context, particularly for colorectal carcinoma, and highlight how a better understanding of the role of the microenvironment has spurred an intense effort to develop novel and innovative strategies for targeting liver metastatic disease, some of which are currently being tested in the clinic.