Highlights of This Issue

Long-term survival is observed in a minority of melanoma patients after treatment with ipilimumab, while the benefit seems to be limited for others. Thus far, no biomarkers are routinely used to predict outcome. In a large multicenter study, Martens and colleagues identified a strong association between baseline frequencies of myeloid-derived suppressor cells and overall survival after start of ipilimumab, translating into a rationale for depletion/inhibition of these cells as therapeutic strategy. Moreover, they propose combination models, including one limited to broadly available routine markers, which strongly correlate with prognosis and suggest predictive impact for outcome after ipilimumab.

Next-generation sequencing (NGS) has redefined the genetic landscape of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. To explore the feasibility of NGS in routine DLBCL patient management, Dubois and colleagues designed the Lymphopanel, a targeted panel based on 34 genes, with a distinct focus on the inclusion of actionable and prognostic targets. The Lymphopanel was informative for 96% of DLBCL patients and offered a clear depiction of DLBCL subtype molecular heterogeneity. The Lymphopanel is a clinically feasible tool, which can stratify patients according to their mutational profiles to afford novel personalized therapy opportunities.

The immune checkpoint inhibitors (ICI) are proven to be effective in cancer immunotherapy; however, the efficacy may be further improved. Ma and colleagues examined the therapeutic effect of a combination of IL18 with ICIs using an animal model of disseminated tumor growth. The results showed that the combination markedly augmented the therapeutic effect. Notably, strong expansion of effector cells, including NK cells and CD8⁺ T cells, and reduction of Treg cells in the tumor microenvironments were observed. There was apparently no adverse effect augmented by the combination. The combination of IL18 and ICIs may be beneficial for cancer immunotherapy.

To build on recent successes in cancer immunotherapy, we need to better understand how the immune system normally contends with cancer. Although the prognostic benefit of tumor-infiltrating T cells is well established, Kroeger and colleagues use innovative immunohistochemical analyses to reveal an equally important role for plasma cells (mature antibody-producing cells) in ovarian cancer. Remarkably, the authors found that the prognostic benefit of T cells is only seen in the presence of plasma cells, suggesting critical interactions between these lymphocyte subsets. The goal now is to develop immunotherapies that promote this potent combination of cellular and humoral responses in patients.