sublingual immunotherapy

Compartment-specific PPARδ activity controls the outcome of cancer-immune cell competition and immunotherapy efficacy.

Bunk Paul P, Ergin Ilgin I, Maher Timothy T, Shah Vyom V et al.

Most patients with solid tumors fail to sustain antitumor immunity, in part because immune cells cannot outcompete cancer cells inside the immunosuppressive tumor microenvironment. Here, we show the lipid-sensing transcription factor PPARδ is a compartment-specific determinant of cancer-immune fitness balance and immunotherapy efficacy. Activating PPARδ in cancer cells promotes their growth and impairs antitumor immunity, whereas activating it in immune cells drives tumor suppression and overrides tumor-promoting effects of cancer-intrinsic activation. Mechanistically, PPARδ enhances CD8+ T cell fitness against cancer through effector-associated chromatin remodeling and Cpt1a-mediated fatty acid oxidation. Therapeutically, PPARδ-activated CD8+ T cells sensitize immunotherapy-resistant microsatellite stable metastatic colorectal cancer to checkpoint blockade in mice, and pharmacological or genetic PPARδ activation enhances human chimeric antigen receptor T cell function. These findings identify compartment-specific PPARδ activity as a targetable driver of immune cell fitness that can be harnessed to improve outcomes in immunotherapy-resistant tumors.

Correction: Linking early and late endpoints in adjuvant immunotherapy trials: an evaluation of multiple clinical outcomes.

Global trends and knowledge evolution of tertiary lymphoid structures in cancer immunotherapy: a bibliometric and visualization analysis.

Li Yanan Y, Cao Zhi Z, Zhou Jingru J, Zhang Yang Y et al.

Tertiary lymphoid structures (TLSs) are ectopic immune aggregates that arise in non-lymphoid tissues during chronic inflammation, including cancer. Their reported associations with antitumor immunity and immune-checkpoint blockade have prompted rapid growth of the field. We therefore mapped the literature on TLSs in cancer immunotherapy over the prespecified period from January 1, 2000 through March 31, 2026. The primary bibliometric corpus comprised 1,373 English-language articles and reviews from the Web of Science Core Collection (WoSCC). PubMed and Scopus were searched independently for descriptive comparison and were not merged with the WoSCC corpus. Analyses used bibliometrix, VOSviewer, CiteSpace, SCImago Graphica, and Microsoft Excel. Publication output rose markedly after 2019 and reached 315 publications in 2025. China, the United States, and France were the leading corresponding-author countries/regions, while INSERM, Sun Yat-sen University, and Fudan University led the distinct-document institutional count. Major mapped themes included B cells, immune-checkpoint blockade, spatial pathology, prognostic modeling, the tumor microenvironment, lymphatic vessels, and high endothelial venules. The independently retrieved PubMed and Scopus datasets showed broadly similar aggregate temporal and title/abstract term profiles. The analysis describes the growth, collaboration structure, and thematic development of TLS research in cancer immunotherapy. These bibliometric patterns indicate research attention; they do not establish biological mechanisms, biomarker performance, therapeutic efficacy, or clinical utility.

Clinical outcomes and prognostic factors after first- and second-line immunotherapy in a cohort of 57 patients with refractory autoimmune encephalitis.

He Jiao J, Lu Haozhe H

Refractory autoimmune encephalitis (AE) is a severe condition with limited real-world evidence on treatment outcomes and prognostic factors. This study evaluated clinical outcomes and factors associated with 6-month functional recovery in a strictly defined refractory AE cohort. This single-center retrospective cohort study screened 246 potentially eligible AE records from 2018 to 2025 and included 57 patients who fulfilled the prespecified refractory AE criteria and had ascertainable 6-month functional outcomes. Second-line immunotherapy was subsequently administered to a subset of patients. The primary outcome was 6-month functional status assessed by the modified Rankin Scale (mRS) after refractory-state adjudication, with favorable outcome defined as mRS 0-2. Multivariable logistic regression, adjusted for baseline severity and constrained by the limited number of unfavorable outcomes, examined factors associated with 6-month functional outcome. All 57 patients fulfilled the harmonized refractory criterion after inadequate response to first-line immunotherapy. Second-line escalation was subsequently administered to 14 patients (24.6%), whereas 43 (75.4%) did not receive second-line therapy. Favorable 6-month outcomes occurred in 9/14 (64.3%) and 28/43 (65.1%), respectively. In the parsimonious multivariable analysis, higher mRS at refractory-state adjudication and ICU admission were associated with unfavorable 6-month functional outcome. The association with ICU admission persisted after adjustment for mRS, but its magnitude was imprecisely estimated and likely overlaps with the underlying construct of disease severity. These findings should therefore be considered exploratory prognostic associations rather than definitive independent predictors.