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Another study showed that the microbiome is predictive not only of response but also of toxicity: the investigators demonstrated that the presence of a certain species of microbe may be protective against the development of colitis from anti–CTLA-4 therapy

-1 and CTLA-4 pathways, comparing combination nivolumab + ipilimumab to the EXTREME regimen as first-line treatment in patients with recurrent/metastatic HNSCC ( ClinicalTrials.gov identifier: NCT02741570). Patients with PD-L1–positive tumors appear

immune-related toxicities after treatment with the CTLA-4 antibody ipilimumab in combination with gemcitabine + cisplatin. 5 This chemoimmunotherapy regimen did not appear to impact OS. Furthermore, another study suggested that chemotherapy may promote

-mediated diarrhea and colitis (IMDC), the second most common irAE, limits the use of ICIs. 5 The incidence and severity of IMDC vary depending on the ICI regimen. Severe forms are attributed to anti–CTLA-4–based regimens, 6 and clinical symptoms range from self

. The gut microbiome is proposed as important to the success of immunotherapy, with most data limited to immune checkpoint inhibitors targeting the PD-1 axis and/or the CTLA-4 axis in melanoma. 3 However, across studies, consistent gut microbiome

(CTLA)-4 targeted therapy. Tremelimumab and ipilimumab are humanized anti–CTLA-4 antibodies currently under investigation in many solid tumors, including prostate cancer. 16 Immune-based therapies pose many challenges, particularly in designing

inhibitors pembrolizumab and nivolumab and the CTLA-4 inhibitor ipilimumab. In the first-line setting, the combination of ipilimumab and nivolumab (ipi/nivo) is the only preferred treatment option for ccRCC using immunotherapy alone in the NCCN Guidelines

hypothesis has also been supported by Herbst et al, 14 who demonstrated associations in tumor expression of PD-L1, T-helper type 1 gene, and CTLA4 , and absence of fractalkine ( CX3CL1 ) in baseline tumors with response rates. The tumor microenvironment

with chemotherapy led to significant response. We showed that neoadjuvant therapy using a single-agent PD-1 inhibitor, combined PD-1/CTLA-4 inhibitors, or PD-1 inhibitor plus FOLFOX combination can be a safe and effective treatment option in selected

, hazard ratio; Ipi, ipilimumab; Nivo, nivolumab; NR, not reached; Pembro, pembrolizumab; RFS, relapse-free survival. In 2014, the CTLA-4 inhibitor ipilimumab became the first approved immunotherapy for the adjuvant treatment of melanoma, but its