Masters of Immunology
Ellen Puré and Albert Lo
Cancer Immunol Res April 1 2016 4 (4) 269-278; DOI:10.1158/2326-6066.CIR-16-0011
Use of immune checkpoint inhibitors is increasing. Some patients with NSCLC treated with nivolumab develop a radiographic cryptogenic organizing pneumonia (COP) pattern of PD-1 inhibitor–related pneumonitis. Recognition of the radiographic pattern is needed for prompt diagnosis and management.
Bleomycin induces DNA damage, which often leads to apoptosis, allowing cell clearance without eliciting an inflammatory response. IL1RA, a potent natural inhibitor of IL1, was released in sufficient amounts upon apoptosis to block the pro-inflammatory effects of IL1.
IFNγ and TNFα are primarily antitumor mediators, but unexpectedly synergized to enhance multiple pathways of immune suppression, using COX2 activation as the intermediary. This mechanism limits type-1 antitumor immunity and provides a rationale for targeting the COX2–PGE2 axis.
Patients who recover from sepsis are immunosuppressed and at higher risk for cancer. Studying melanoma in post–septic-shock mice revealed that tumor composition, progression rate, and microenvironment were biased toward attracting tumor-associated macrophages that support tumor growth.
Many tumors express receptors for the vitamin folate (FRs). Folate-conjugated IgG, which can bind both FR+ tumors and NK-cell receptors for IgG, induced potent NK-cell antitumor responses that were further augmented by cytokine therapy.
BCL6 supports the growth of DLBCL. Expression of the microRNA miR-144 in DLBCL cells inversely correlated with BCL6 expression. miR-144 inhibited BCL6 expression, affecting DLBCL proliferation and invasiveness. Thus, miR-144 should be considered in approaches to this cancer.
Patients experiencing dose-limiting adverse effects after progressing on ipilimumab were enrolled in a trial of nivolumab. Nivolumab was active, safe and may not be needed indefinitely. The presence of fewer pretreatment myeloid-derived suppressor cells was associated with better responses and survival.
Mutant KRAS uses cell-intrinsic mechanisms to promote aggressive tumor growth. Now, mutated KRAS has been found to use cell-extrinsic mechanisms early in tumorigenesis that induce Tregs and immune evasion through activating the MEK–ERK–AP1 pathway, producing IL10 and TGFβ
It is not clear which patients with mCRC will benefit from treatment with cetuximab, an antibody to the EGF receptor. Cetuximab-mediated ADCC and NK-cell cytotoxicity ex vivo correlated with FcγR polymorphisms and could predict cetuximab responsiveness.