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Unravelling the details of range expansion and ecological dominance shifts of insect pests has been challenging due to the lack of basic knowledge about population structure, gene flow, and most importantly, how natural selection is affecting the adaptive process. Piezodous guildinii is an emerging pest of soybean in the southern region of the United States, and increasingly important in Brazil in recent years. However, the reasons P. guildinii is gradually becoming more of a problem are questions still mostly unanswered. Here, we have genotyped P. guildinii samples and discovered 1,337 loci containing 4,083 variant sites SNPs that were used to estimate genetic structure and to identify gene candidates under natural selection. Our results revealed the existence of a significant genetic structure separating populations according to their broad geographic origin, i.e., U.S. and Brazil, supported by AMOVA (FGT = 0.26), STRUCTURE, PCA, and FST analyses. High levels of gene flow or coancestry within groups (i.e., within countries) can be inferred from the data, and no spatial pattern was apparent at the finer scale in Brazil. Samples from different seasons show more heterogeneous compositions suggesting mixed ancestry and a more complex dynamic. Lastly, we were able to detect and successfully annotated 123 GBS loci (10.5%) under positive selection. The gene ontology (GO) analysis implicated candidate genes under selection with genome reorganization, neuropeptides, and energy mobilization. We discuss how these findings could be related to recent outbreaks and suggest how new efforts directed to better understand P. guildinii population dynamics.

Jason M. Redman, Jay Friedman, Yvette Robbins, Cem Sievers, Xinping Yang, Wiem Lassoued, Andrew Sinkoe, Antonios Papanicolau-Sengos, Chyi-Chia Lee, Jennifer L. Marte, Evrim Turkbey, Wojtek Mydlarz, Arjun Joshi, Nyall R. [...]

BACKGROUND. Head and neck squamous cell carcinoma not associated with HPV (HPV-unrelated HNSCC) is associated with a high rate of recurrence and poor survival. METHODS. We conducted a clinical trial in 14 patients with newly diagnosed HPV-unrelated HNSCC to evaluate the safety and efficacy of neoadjuvant bintrafusp alfa, a bifunctional fusion protein that blocks programmed death ligand 1 (PD-L1) and neutralizes TGF-[beta]. RESULTS. Bintrafusp alfa was well tolerated, and no treatment-associated surgical delays or complications occurred. Objective pathologic responses (PRs) were observed, and 12 of the 14 (86%) patients were alive and disease free at 1 year. Alterations in Treg infiltration and spatial distribution relative to proliferating [CD8.sup.+] T cells indicated a reversal of Treg immunosuppression in the primary tumor. Detection of neoepitope-specific tumor T cell responses, but not virus-specific responses, correlated with the development of a PR. Detection of neoepitope-specific responses and PRs in tumors was not correlated with genomic features or tumor antigenicity but was associated with reduced pretreatment myeloid cell tumor infiltration. These results indicate that dual PD-L1 and TGF-[beta] blockade can safely enhance tumor antigen-specific immunity and highlight the feasibility of multimechanism neoadjuvant immunotherapy for patients with HPV-unrelated HNSCC. CONCLUSION. Our s0tudies provide insight into the ability of neoadjuvant immunotherapy to induce polyclonal neoadjuvant-specific T cell responses in tumors and suggest that features of the tumor microenvironment, such as myeloid cell infiltration, may be a major determinant of enhanced antitumor immunity following such treatment. TRIAL REGISTRATION. ClinicalTrials.gov NCT04247282. FUNDING. This work was funded by the Center for Cancer Research, the NCI, and the Intramural Research Program of the NIDCD, NIH. Bintrafusp alfa was provided by the health care business of Merck KGaA (Darmstadt, Germany), through a Cooperative Research and Development Agreement with the NCI. Additional funding was provided by ImmunityBio through a Cooperative Research and Development Agreement with the NIDCD., Introduction Oncologic outcomes following standard-of-care treatment of newly diagnosed, advanced-stage head and neck squamous cell carcinoma not associated with HPV (HPV-unrelated HNSCC) are poor, with disease relapse occurring in approximately [...]

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs., Introduction Immunosuppression is an accepted hallmark of tumor progression, and targeting immune-suppressive pathways has led to enhanced patient survival in multiple cancers, including head and neck cancer (HNC) (1, 2). [...]

Introduction: Cancer stem cells (CSCs), a group of tumor-initiating and tumormaintaining cells, may be major players in the treatment resistance and recurrence distinctive of chordoma. Characterizing CSCs is crucial to better targeting this subpopulation. Methods: Using flow cytometry, six chordoma cell lines were evaluated for CSC composition. In vitro, cell lines were stained for B7H6, HER2, MICA-B, ULBP1, EGFR, and PD-L1 surface markers. Eighteen resected chordomas were stained using a multispectral immunofluorescence (mIF) antibody panel to identify CSCs in vivo. HALO software was used for quantitative CSC density and spatial analysis. Results: In vitro, chordoma CSCs express more B7H6, MICA-B, and ULBP1, assessed by percent positivity and mean fluorescence intensity (MFI), as compared to non-CSCs in all cell lines. PD- L1 percent positivity is increased by >20% in CSCs compared to non-CSCs in all cell lines except CH22. In vivo, CSCs comprise 1.39% of chordoma cells and most are PD-L1+ (75.18%). A spatial analysis suggests that chordoma CSCs cluster at an average distance of 71.51mm (SD 73.40 mm) from stroma. Discussion: To our knowledge, this study is the first to identify individual chordoma CSCs and describe their surface phenotypes using in vitro and in vivo methods. PD-L1 is overexpressed on CSCs in chordoma human cell lines and operative tumor samples. Similarly, potential immunotherapeutic targets on CSCs, including B7H6, MICA-B, ULBP1, EGFR, and HER2 are overexpressed across cell lines. Targeting these markers may have a preferential role in combating CSCs, an aggressive subpopulation likely consequential to chordoma's high recurrence rate. [ABSTRACT FROM AUTHOR]

Background: De‐escalation strategies for newly‐diagnosed p16‐positive oropharyngeal squamous cell carcinoma (p16+ OPSCC), aim to reduce treatment‐related morbidity without compromising disease control. One strategy is neoadjuvant cisplatin and docetaxel chemotherapy (NAC + S) before transoral robotic surgery, with pathology‐based risk‐adapted adjuvant treatment. Methods: We examined the recurrence‐free survival (RFS) for patients who received NAC + S. Results: Comparing outcomes in 103 patients between 2008 and 2023, 92% avoided adjuvant treatment and showed significantly higher 2‐year recurrence‐free survival (RFS) compared to those with adjuvant treatment (95.9% vs. 43.8%, p = 0.0049) Conclusion: Our findings suggest that pathology‐based risk‐adapted omission of adjuvant treatment following NAC + S does not appear to elevate recurrence risk and that NAC may identify patients with favorable tumor biology, yielding a 2‐year RFS probability exceeding 95% without adjuvant treatment. Further, the study identifies a patient subset experiencing disease recurrence despite triple modality therapy. Despite limitations, including a retrospective design and modest sample size, the data advocate for controlled NAC + S studies. [ABSTRACT FROM AUTHOR]

This article discusses the characterization of cancer stem cells (CSCs) in olfactory neuroblastoma (ONB), a rare malignant neoplasm. The study aimed to identify the density of CSCs and PD-L1 expression in ONB using immunofluorescence. The results showed that CSCs were present in ONB, but they were uncommon and did not correlate with grade, stage, or recurrence. However, a significant number of CSCs expressed PD-L1, suggesting a potential immunotherapy strategy for ONB by targeting this cell population through PD-1/PD-L1 immune checkpoint blockade. [Extracted from the article]