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Human Papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with radiotherapy, alone or combined with immune checkpoint inhibitors, often failing to achieve durable disease control. Here, by conducting longitudinal multi-omic analyses of pre- and post-radiation biopsies from patients receiving a pre-operative hypofractionated radiation regimen, we uncover that radiation rapidly depletes a subpopulation of tumor-infiltrating lymphocytes (TIL), characterized by a proliferative, cytotoxic, and tissue-resident gene signature (T Prolif_Tox ). We provide multi-dimensional evidence for tumor antigen-specificity of T Prolif_Tox clonotypes and show that post-radiation tumors are instead repopulated by regulatory and non-specific clones. Finally, TIL depletion correlates with radiorecurrent disease after conventional radiation, emphasizing the potential impact of radiation-induced TIL loss regardless of fractionation. Thus, this study provides key insights into radiotherapy-induced alterations in the immune microenvironment that drive immunologic radioresistance and proposes restoring tumor antigen-specific T cell clonotypes as a strategy to improve radioimmunotherapy responses in HNSCC. Combining radiation therapy (RT) with immunotherapy has had limited therapeutic benefits in the treatment of head and neck cancer (HNSCC). Here, the authors present a multi-omics analysis of patient biopsies pre- and post- hypofractionated RT and uncover RT-mediated depletion of tumor-reactive CD8+ T cells as the underlying cause of immunologic radioresistance in HNSCC.

Heat tolerance is an important trait in cowpea, a crop that constitutes the primary protein source for a large portion of the human population in sub-Saharan Africa. Cowpea grows across this region, with cultivated, landrace, semi-wild, and wild cowpeas germplasm growing across diverse climatic conditions. This study used environmental association (envGWAS) and allele frequency outlier approaches in a panel of 580 gene bank accessions to identify genomic regions associated with heat and limited precipitation. Because allele frequency outliers are detected independent of potential selection factors driving differentiation, we used a ranking-based approach to identify the climate variables most associated with variants among outliers. Precipitation-related variables dominated the signals we identified for envGWAS and allele frequency outliers. We found variants on all eleven chromosomes putatively associated with the adaptation of cowpea to higher-temperature environments. The considerable overlap between variants associated with low precipitation and high temperature suggests that these traits may be inextricably linked in cowpea. The Sahel region is the source of many accessions with derived variants associated with high temperature, suggesting the potential for accessions from this region to contribute to heat tolerance alleles for cowpea improvement.