Volume 3 Issue 9, September 2022

The identification of tumor-reactive T cells using phenotypic markers is now well established in treatment-naive tumors. It is unclear, however, whether these markers can also be useful after immune checkpoint blockade (ICB). A new study finds that CXCL13 expression robustly identifies tumor-reactive T cells before and after ICB and is associated with treatment response.

Increasing evidence links RNA methyltransferases to DNA damage repair. METTL16 is now shown to antagonize homologous recombination by preventing DNA-end resection via MRE11. Thus, METTL16 may represent a cancer vulnerability that can be used to identify patients able to benefit from combination therapies with DNA-damaging agents.

Therapeutic resistance in prostate cancer can be driven by lineage plasticity, but the mechanisms behind this are unclear, and therapies to prevent or reverse the process are nonexistent. A new study reveals the JAK/STAT signaling axis as a driver of lineage plasticity with tremendous therapeutic potential.

Many patients with colorectal cancer (CRC) relapse after chemotherapy. Tumor cells that do not completely adapt to their environment (owing to an incomplete set of CRC driver mutations) enter a latent state, in which the expression of Mex3a is upregulated. Mex3a⁺ cells are chemoresistant and reactivate after treatment, which leads to regeneration of the disease.

Schmatko et al. review the application of artificial intelligence to digitized histopathology for cancer diagnosis, prognosis and classification and discuss its potential utility in the clinic and broader implications for cancer research and care.

Walle & Bajaj et al. assess the frequency of cytokine release syndrome upon COVID-19 vaccination in patients with cancer receiving immune-checkpoint inhibitors and find that while elevated cytokines levels are common, they do not manifest in detectable CRS.

Batlle and colleagues report that after chemotherapy, Mex3a⁺ colorectal cancer cells represent drug-tolerant persister cells that lead to recurrence by downregulating the WNT–Lgr5⁺ stem cell program and adopting a transient regenerative state.

Mu and colleagues describe a JAK–STAT signaling-dependent transition to a stem-like, multilineage state that is resistant to prostate cancer AR therapy and propose combinatorial targeting of JAK–STAT proteins to resensitize resistant tumors.

Lou and colleagues describe the role of METTL16 in homologous recombination repair and demonstrate that PARP inhibition may be beneficial in the treatment of PDAC that is characterized by high METTL16.

Xi and colleagues show that BMP signaling has tumor-suppressive effects in ACVR1 wild-type diffuse intrinsic pontine glioma by modulating stemness via chromatin regulation of CXXC5, and demonstrate the therapeutic potential of this pathway using in vivo mouse models.

Zhang and colleagues analyze single-cell data from patients treated with immunotherapy in five cancer types and find that CXCL13-expressing subsets are implicated in response to treatment in the CD8⁺ and CD4⁺ T cell compartments.