What We're Reading
Cancer Immunol Res February 1 2017 5 (2) 93-93;
This case report provides a rationale for a carefully timed combination of WBRT + anti-PD-1 for the treatment of metastatic melanoma patients with brain metastases, as well as for other cancers for which anti–PD-1 has been approved.
PD-L1 induction on tumor cells is IFNγ-dependent and transient, but becomes IFNγ-independent and long-lived on tumorassociated macrophages. Thus, assessing PD-L1 expression on both tumor and host cells may better stratify patients undergoing PD-1/PD-L1 blockade therapy.
Patients whose tumors express PD-1 and PD-L1 are more likely to respond to PD-1 blockade. Patients with synovial sarcoma were found to coordinately express PD-1, PD-L1, and CD8, providing a rationale for their treatment with PD-1/PD-L1 inhibitors.
Tumor-specific CD8+ T cells temporarily control tumor growth, but eventually tumors can escape. Adoptive transfer of tumor-recognizing CD4+ T cells rescued the function of exhausted CD8+ T cells through co-cross-presentation by stroma, which led to complete tumor eradication.
Merkel cell carcinoma patients had improved survival if their tumors contained a greater frequency or diversity of T cells that were specific for a prevalent Merkel cell polyomavirus epitope. Thus, transgenic T-cell receptor therapy could potentially benefit patients.
The TCR repertoire of T lymphocytes from breast tumors, draining lymph nodes (LNs), and adjacent tissues were compared. Tumor-positive LNs had greater T-cell clonal expansion and more T-cell infiltration of tumors, illustrating exchange between the two compartments.
Tyrosine kinase inhibitors (TKIs) are used therapeutically to inhibit aberrant oncokinase signaling in tumor cells. Several mouse solid-tumor models showed that the TKI dasatinib has off-target immunostimulatory effects, which could be important in the control of tumors.
Four parameters were identified—CD8+ TILs, galectin-3+ tumors, galectin-9+ DCs, and a high M1/M2 ratio—whose combined presence was prognostic for long-term survival and predictive for sustained clinical benefit from adoptive T cell transfer in stage IV melanoma.