What We're Reading
Cancer Immunol Res May 1 2019 7 (5) 695-695;
Most patients with metastasis of large bowel cancer do not benefit from immune therapy. This case study shows that a rare gene mutation, termed 9p24.1 copy-number gain, in this otherwise incurable tumor provoked a response to immune therapy.
The lectin Siglec-9 can regulate TCR signaling and effector function of human cytotoxic CD8+ T cells. Siglec-9 expression defines a subset of effector memory CD8+ T cells that is prevalent in melanoma tissues.
Evaluation of MHC class-I binding predictors based on experimentally validated binders revealed that individual thresholds are needed for different HLA types and peptide lengths to optimize sensitivity and increase the number of epitopes as potential targets for immunotherapy.
Gastric cancer TME infiltration patterns were determined and systematically correlated with TME cell phenotypes, genomic traits, and patient clinicopathological features to establish the “TMEscore.” This score was a prognostic and predictive factor for immune checkpoint blockade response.
For nonmetastatic colorectal cancer, FoxP3+ and CD3+ T-cell densities have prognostic value up to stage III is reached. Loss of prognostic value at that point indicates that various T-cell subsets are differentially influential as the cancer progresses.
IL15 promotes metabolically fit CAR-T cells with a lessdifferentiated stem cell memory phenotype. Addition of IL15 is a clinically translatable method for improving the antitumor function of ex vivo expanded CAR-T cells, which could improve outcomes for patients.
CAR T-cell antitumor therapy fails when the tumor loses expression of the chosen epitope. Receptors that mimic antibodies and that recognize two epitopes may reduce the chances for tumor cells to escape immune surveillance.
TGFβ stimulation of activated CD8+ T cells from cancer patients induces upregulation of CD103 and CXCL13, which is important for tertiary lymphoid structure formation. The data highlight a role for TGFβ in coordinating immune responses against tumors.
MHC-bound peptides derived from aberrant proteins may be an immunotherapeutic target on cancer cells. However, T cells recognizing such an antigen failed to react against leukemic cells. Thus, concern is warranted for immunotherapies targeting such antigens.
The expression of immune checkpoint molecules PD-1, PD-L1, B7-H3, and IDO in fibrolamellar carcinoma (FLC) is related to CD8+ T-cell density. These checkpoints are clinically targetable with inhibitors. Thus, using immune checkpoint blockade may be efficacious in FLC.
A conserved long noncoding RNA (lncRNA), pseudogene Olfr29-ps1, was identified and shown to be induced under inflammatory conditions and in melanomas. Olfr29-ps1 can regulate the immunosuppressive function and differentiation of monocytic MDSCs both in vitro and in vivo.
Suboptimal antitumor immunotherapy increases genomic instability in tumor cells by inducing APOBEC3. Resulting mutations can promote tumor cell escape from co-applied therapies. Immunotherapies should be optimized early to prevent a direct enhancement of tumor cell escape.
CCR7+NK cells and CCL19 increased as melanoma progressed. Melanoma-derived cancer stem cells overexpressed CCR7 and were efficiently recognized and killed by NK cells. CCR7 may be a biomarker for metastatic melanoma.