2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T54d,Immune checkpoint blockade-based multimodal therapy is widely used across oncology; yet drivers of resistance in most cancer types are not well understood. Here, we comprehensively characterized the tumor genome, microenvironment and microbiome in a phase 3 international randomized trial ( NCT02952586 ) to identify factors that shape outcomes to anti-PD-L1 avelumab plus standard-of-care chemoradiotherapy versus placebo/chemoradiotherapy in individuals with locally advanced head and neck cancer. Patients receiving avelumab whose tumors contained distinct immunologic and genetic features had superior outcomes compared to those receiving placebo. By contrast, patients with increased myeloid/neutrophil activities had worse outcomes with avelumab than those treated with placebo. Strikingly, these tumors possessed telltale intratumoral bacteria, elevated tumor-associated neutrophils, high systemic neutrophil-to-lymphocyte ratios and suppressed adaptive immunity. We define tumor ecosystems associated with benefit to chemoimmunotherapy. Our data demonstrate how intratumoral bacteria affect immune checkpoint blockade response within a randomized trial. These discoveries enhance our understanding of combination immunotherapy, provide a useful multiomic resource and identify unanticipated interactions that may guide future therapeutic strategies.31:T8a2,Tertiary lymphoid structures (TLS) are ectopic lymphoid formations within or around tumours, emerging as important predictors of prognosis and response to immune checkpoint inhibitors (ICI) in various cancers. However, in Merkel cell carcinoma (MCC), the correlation between TLS and ICI response has not yet been evaluated. Furthermore, the criteria for assessing TLS maturity vary by report, and there is no unified consensus. In this study, we investigated the relationship between TLS and ICI responsiveness in MCC using spatial proteomics at the single-cell level. By comparing the spatial characteristics of TLS in ICI responders and non-responders, we also aimed to identify features related to functionality of TLS, distinct from the previously reported maturity of TLS. We analysed 24 TLSs from 13 MCC cases treated with the anti-PD-L1 antibody, avelumab, employing the PhenoCycler platform with 16 oligonucleotide-labeled antibodies. Infiltrating immune cells and tumour cells were phenotyped based on machine learning, and spatial single-cell analysis was performed, including cellular neighbourhood analysis and cell-cell correlation analysis. Our findings revealed that the number of TLS positively correlated with survival and ICI response (p=0.0274). The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. Furthermore, it was found that CD8-positive T cells and CD4-positive T cells approaching B cells expressed PD1. This study demonstrated a significant positive correlation between the number of TLS and ICI response in MCC. Additionally, our results suggest that the immune composition and spatial configuration within TLS may be important determinants of ICI efficacy.32:Tbb6,Abstract Background Tertiary lymphoid structures (TLS) are ectopic lymphoid formations within or around tumours, emerging as important predictors of prognosis and response to immune checkpoint inhibitors (ICI) in various cancers. However, in Merkel cell carcinoma (MCC), the correlation between TLS and ICI response has not yet been evaluated. Furthermore, the criteria for assessing TLS maturity vary by report, and there is no unified consensus. Objective In this study, we investigated the relationship between TLS and ICI responsiveness in MCC using spatial proteomics at the single-cell level. By comparing the spatial characteristics of TLS in ICI responders and non-responders, we also aimed to identify features related to functionality of TLS, distinct from the previously reported maturity of TLS. Methods We analysed 24 TLSs from 13 MCC cases treated with the anti-PD-L1 antibody, avelumab, employing the PhenoCycler platform with 16 oligonucleotide-labeled antibodies. Infiltrating immune cells and tumour cells were phenotyped based on machine learning, and spatial single-cell analysis was performed, including cellular neighbourhood analysis and cell-cell correlation analysis. Results Our findings revealed that the number of TLS positively correlated with survival and ICI response (p=0.0274). The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. Furthermore, it was found that CD8-positive T cells and CD4-positive T cells approaching B cells expressed PD1. Conclusions This study demonstrated a significant positive correlation between the number of TLS and ICI response in MCC. Additionally, our results suggest that the immune composition and spatial configuration within TLS may be important determinants of ICI efficacy. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"avelumab: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on avelumab (generic). Clinician-written summaries and actionable practice insights. 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The exact number was not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"warning","value":"Study design is a cross-trial indirect comparison using a weighted hazard modeling approach — not a randomized head-to-head trial. Level of evidence assigned accordingly.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.06.004","tag_type":"warning","value":"The assumption that 100% of eligible PBC patients receive avelumab maintenance likely represents a best-case scenario for the comparator arm, potentially underestimating EV+P's true real-world advantage.","value_numeric":null}],"summaries":{"what_studied":"This modeling study compared first-line enfortumab vedotin + pembrolizumab (EV+P, from EV-302) versus platinum-based chemotherapy ± avelumab maintenance (from JAVELIN Bladder-100) in locally advanced/metastatic urothelial carcinoma (la/mUC), using a hybrid approach that applied JB-100 avelumab hazard ratios to EV-302 PBC patients without progression.","key_result":"EV+P significantly improved both PFS (HR 0.51, 95% CI 0.44–0.59) and OS (HR 0.64, 95% CI 0.49–0.86) versus the modeled PBC ± avelumab arm, with results consistent across sensitivity analyses.","limitations":"- The model assumes **all** patients without progression received avelumab, which likely overestimates real-world avelumab uptake and may favor the PBC arm.\n- Comparison relies on cross-trial modeling (patient-level EV-302 data combined with study-level JB-100 data), not a head-to-head RCT.\n- Avelumab was approved after EV-302 initiation, so its use in that trial was potentially underrepresented.","practice_takeaway":"EV+P offers meaningful PFS and OS gains over platinum-based chemotherapy even when avelumab maintenance is assumed for all eligible patients, supporting EV+P as the preferred first-line standard of care in la/mUC. Clinicians choosing between these regimens need not wait to see if patients respond to chemotherapy before acting on this evidence."}},{"doi":"10.1038/s43018-025-01068-0","pmid":"41482527","title":"Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer","journal_title":"Nature Cancer","journal_issn":"2662-1347","published_at":"2026-01-03T00:00:00.000Z","url":"https://doi.org/10.1038/s43018-025-01068-0","source_score":180,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-05","doi":"10.1038/s43018-025-01068-0","days":"30","issn":"2662-1347","rank":"7","field":"Clinical Medicine","score":"180","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1038/s43018-025-01068-0","title":"Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer.","journal":"Nature cancer","methods":"","results":"","abstract":"$30","keywords":[],"pubmed_id":"41482527","conclusions":"","publication_date":"2026-01-03T00:00:00"},"crossref":{"DOI":"10.1038/s43018-025-01068-0","URL":"https://doi.org/10.1038/s43018-025-01068-0","ISSN":["2662-1347"],"link":[{"URL":"https://www.nature.com/articles/s43018-025-01068-0.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s43018-025-01068-0","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s43018-025-01068-0.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer"],"author":[{"given":"Nadeem","family":"Riaz","sequence":"first","affiliation":[]},{"given":"Tyler J.","family":"Alban","sequence":"additional","affiliation":[]},{"given":"Robert I.","family":"Haddad","sequence":"additional","affiliation":[]},{"given":"Michelle","family":"Saul","sequence":"additional","affiliation":[]},{"given":"Vladimir","family":"Makarov","sequence":"additional","affiliation":[]},{"given":"Yingjie","family":"Zhu","sequence":"additional","affiliation":[]},{"given":"Ezra E. W.","family":"Cohen","sequence":"additional","affiliation":[]},{"given":"Robert L.","family":"Ferris","sequence":"additional","affiliation":[]},{"given":"Peter Mu-Hsing","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Jin-Ching","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Amanda","family":"Psyrri","sequence":"additional","affiliation":[]},{"given":"Prerana Bangalore","family":"Parthasarathy","sequence":"additional","affiliation":[]},{"given":"Ardijana","family":"Novaj","sequence":"additional","affiliation":[]},{"given":"Mruniya","family":"Gawali","sequence":"additional","affiliation":[]},{"given":"Douglas","family":"Hoen","sequence":"additional","affiliation":[]},{"given":"Phineas","family":"Hamilton","sequence":"additional","affiliation":[]},{"given":"Natalie L.","family":"Silver","sequence":"additional","affiliation":[]},{"given":"Ivan","family":"Juric","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Chawla","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Gradissimo","sequence":"additional","affiliation":[]},{"given":"Jennifer","family":"Ko","sequence":"additional","affiliation":[]},{"given":"Daniel J.","family":"McGrail","sequence":"additional","affiliation":[]},{"given":"Craig B.","family":"Davis","sequence":"additional","affiliation":[]},{"given":"Nancy Y.","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Timothy A.","family":"Chan","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,1,2]]},"member":"297","prefix":"10.1038","source":"Crossref","volume":null,"created":{"date-time":"2026-01-02T10:01:47Z","timestamp":1767348107000,"date-parts":[[2026,1,2]]},"indexed":{"date-time":"2026-01-02T17:28:05Z","timestamp":1767374885129,"date-parts":[[2026,1,2]]},"license":[{"URL":"https://www.springernature.com/gp/researchers/text-and-data-mining","start":{"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000,"date-parts":[[2026,1,2]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.springernature.com/gp/researchers/text-and-data-mining","start":{"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000,"date-parts":[[2026,1,2]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://www.nature.com/articles/s43018-025-01068-0"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"9 September 2024"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"6 October 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"2 January 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":1,"value":"T.A.C. is a cofounder of Gritstone Oncology and holds equity. T.A.C. also holds equity in An2H. T.A.C. acknowledges grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H and Eisai. T.A.C. has served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca and An2H. T.A.C. is an inventor on intellectual property held by Memorial Sloan Kettering Cancer Center on using TMB to predict immunotherapy response, with pending patent, which has been licensed to PGDx. T.A.C. is on the advisory board of Cell. N.R. acknowledges research support from Pfizer, REPARE Therapeutics, Invitae and Bristol-Myers Squibb. The other authors declare no competing interests."}],"deposited":{"date-time":"2026-01-02T10:01:49Z","timestamp":1767348109000,"date-parts":[[2026,1,2]]},"issn-type":[{"type":"electronic","value":"2662-1347"}],"published":{"date-parts":[[2026,1,2]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.1056/NEJMoa1602252","key":"1068_CR1","year":"2016","issue":null,"author":"RL Ferris","volume":"375","first-page":"1856","unstructured":"Ferris, R. L. et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 375, 1856–1867 (2016).","article-title":null,"journal-title":"N. Engl. J. Med.","doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(19)32591-7","key":"1068_CR2","year":"2019","issue":null,"author":"B Burtness","volume":"394","first-page":"1915","unstructured":"Burtness, B. et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394, 1915–1928 (2019).","article-title":null,"journal-title":"Lancet","doi-asserted-by":"publisher"},{"DOI":"10.1126/science.aar4060","key":"1068_CR3","year":"2018","issue":null,"author":"A Ribas","volume":"359","first-page":"1350","unstructured":"Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018).","article-title":null,"journal-title":"Science","doi-asserted-by":"publisher"},{"DOI":"10.1038/nrd.2018.210","key":"1068_CR4","year":"2018","issue":null,"author":"J Tang","volume":"17","first-page":"854","unstructured":"Tang, J. et al. Trial watch: the clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nat. Rev. Drug Discov. 17, 854–855 (2018).","article-title":null,"journal-title":"Nat. Rev. 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The number of TLS observed within the tumour was significantly higher in responders than in non-responders (p=0.0043). Cellular neighbourhood analysis and cell-cell correlation analysis demonstrated that in functional TLS in responder cases, T cells infiltrated densely within B cell clusters, extending close to follicular dendritic cells, and CD4-positive T cells adjacent to CD8-positive T cells express PD1. In contrast, in non-responder TLS, although B cell density is high, T cells did not infiltrate into B cell cluster areas but instead resided in the peripheral areas. 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