RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma.

Background: Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear.

Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.

Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.

Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis.

Mitochondrial DNA (mtDNA) mutations are frequent in cancer, yet their precise role in cancer progression remains debated. To functionally evaluate the impact of mtDNA variants on tumor growth and metastasis, we developed an enhanced cytoplasmic hybrid (cybrid) generation protocol and established isogenic human melanoma cybrid lines with wild-type mtDNA or pathogenic mtDNA mutations with partial or complete loss of mitochondrial oxidative function. Cybrids with homoplasmic levels of pathogenic mtDNA reliably established tumors despite dysfunctional oxidative phosphorylation.

Cranioencephalic functional lymphoid units in glioblastoma.

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8 T cell clonotypes in the CB that were also found in the tumor.