The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.Galectins are an endogenous family of β-galactoside-binding proteins that play complex and multifaceted roles at various stages of cancer progression, including modulation of tumor cell proliferation, signaling, adhesion, migration, invasion, epithelial-mesenchymal transition, angiogenesis, and immune escape. Recently, galectins have been implicated as major therapeutic determinants that confer sensitivity or resistance to a wide range of anticancer modalities including chemotherapy, radiotherapy, targeted therapies, antiangiogenic therapies, and immunotherapies. Here, we present an integrated approach to the pleiotropic functions of galectins and discuss their emerging roles with respect to mechanisms of resistance or sensitivity to anticancer therapies. Taken together, these findings suggest that targeting galectins and/or their glycosylated ligands may help to overcome resistance and to increase the clinical efficacy of anticancer strategies.
mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established.

To characterize
alterations in NSCLC, we analyzed the genomic, protein expression, and clinical outcome data of patients with
alterations treated at Memorial Sloan Kettering.

In 4,813 tumors from patients with NSCLC, we identified 8% (
= 407) of patients with
-mutant lung cancer. We describe two categories of
mutations class 1 mutations (truncating mutations, fusions, and homozygous deletion) and class 2 mutations (missense mutations). Protein expression loss was associated with class 1 mutation (81% vs. 0%,
< 0.001). Both classes of mutation co-occurred more frequently with
, and
mutations compared with
wild-type tumors (
< 0.001). In patients with metastatic NSCLC,
alterations were associated with shorter overall survival, with class 1 alterations associated with shortest suRCA4-mutant lung cancers may be more sensitive to immunotherapy.
In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. Here, we assess PD-L1 expression on both tumor and immune cells using quantitative immunofluorescence to assess association with benefit from neoadjuvant durvalumab concurrent with chemotherapy in TNBC.

Pretreatment core needle biopsies (
= 69) were obtained from patients who participated in a phase I/II clinical trial (NCT02489448). The final analysis included 45 patients [pathologic complete response (pCR) = 18, non-pCR = 27] due to technical issues and insufficient tissue. Slides were stained using a previously validated Ultivue DNA-based Ultimapper kit (CD8, CD68, PD-L1, Cytokeratin/Sox10, and Hoechst counterstain). The PD-L1 expression was analyzed by molecular compartmentalization without segmentation using AQUA software (version 3.2.2.1) in three tissue compartments including tumor (cytokeratin-positive cells), CD68
cells, and overall stroma.

In patients with pCR, PD-L1 expression was significantly higher in tumor cells, in CD68
cells and in the stroma compared with patients non-pCR. There was no difference in the amount of CD68
cells in the tumor or stromal compartments between cases with pCR and non-pCR.

Expression of PD-L1 in tumor cells, immune cells in stroma, and colocalized with CD68
cells is associated with higher rates of pCR to durvalumab and chemotherapy in TNBC.
Expression of PD-L1 in tumor cells, immune cells in stroma, and colocalized with CD68+ cells is associated with higher rates of pCR to durvalumab and chemotherapy in TNBC.
Reliable predictive and prognostic markers are still lacking for patients treated with programmed death receptor 1 (PD1) inhibitors for non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic and predictive values of different baseline metabolic parameters, including metabolic tumor volume (MTV), from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (
F-FDG PET/CT) scans in patients with NSCLC treated with PD1 inhibitors.

Maximum and peak standardized uptake values, MTV and total lesion glycolysis (TLG), as well as clinical and biological parameters, were recorded in 75 prospectively included patients with NSCLC treated with PD1 inhibitors. Associations between these parameters and overall survival (OS) were evaluated as well as their accuracy to predict early treatment discontinuation (ETD).

A high MTV and a high TLG were significantly associated with a lower OS (p<0.001). The median OS in patients with MTV above the median (36.5 cm
) was 10.5 months (95% CI 6.2 to upper limit unreached), while the median OS in patients with MTV below the median was not reached. https://www.selleckchem.com/products/AZD6244.html Patients with no prior chemotherapy had a poorer OS than patients who had received prior systemic treatment (p=0.04). MTV and TLG could reliably predict ETD (area under the receiver operating characteristic curve=0.76, 95% CI 0.65 to 0.87 and 0.72, 95% CI 0.62 to 0.84, respectively).

MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine
F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.
MTV is a strong prognostic and predictive factor in patients with NSCLC treated with PD1 inhibitors and can be easily determined from routine 18F-FDG PET/CT scans. MTV, could help to personalize immunotherapy and be used to stratify patients in future clinical studies.