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-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

PARP, IDO, MEK, HDAC, and CTLA4. Immunologic agents are being evaluated in the adjuvant and neoadjuvant settings, including for their benefit in eradicating residual disease postoperatively. Promising Novel Approaches Many novel strategies are

immune checkpoint blockade . N Engl J Med 2018 ; 378 : 158 – 168 . 29320654 10.1056/NEJMra1703481 8. Gupta A , De Felice KM , Loftus EV Jr , . Systematic review: colitis associated with anti-CTLA-4 therapy . Aliment Pharmacol Ther 2015

which MMRd tumors evade immune-mediated killing is through upregulating immune checkpoints, such as PD-1 and CTLA-4. As a result, MMRd tumors are preferentially sensitive to immune checkpoint inhibitors (ICIs), which reactivate the antitumor immune

mutation is chemotherapy + anti–PD-1 (nivolumab) + CTLA-4 (ipilimumab) for 2 cycles. 21 A randomized study of 719 patients found that chemotherapy + 2 cycles of nivolumab/ipilimumab improved OS regardless of PD-L1 status: median OS was 14 versus 10