Abstract A010: B cell infiltration and clonal expansion in tertiary lymphoid structures: Insights from intravital microscopy
Notice bibliographique
Résumé
Abstract Emerging clinical evidence highlights the importance of tumor infiltration of activated immune cells, particularly T and B lymphocytes, for the efficacy of immune-based cancer therapies. However, many patients show limited immune cell presence in the tumor microenvironment. High endothelial venules (HEVs) are specialized blood vessels that enable lymphocyte trafficking from circulation into lymph nodes or tumors. Histological analyses of clinical tumor samples indicate that HEVs are positioned near dense aggregates of B and T lymphocytes, known as tertiary lymphoid structures (TLS), underscoring their role in immune cell recruitment and anti-tumor immunity. The abundant development of TLS and HEVs is associated with clinical response to immune checkpoint inhibition therapy and cancer survival. Recently, we found that simultaneous activation of innate immune effectors, STING and lymphotoxin-β receptor (LTβR) using their agonists induces the formation of TLS and HEVs in TLS/HEV-free tumors. In the current study, mouse pancreatic ductal adenocarcinoma (KPC) tumors were grown in the dorsal skin fold window chamber (DSWC) and received STING/LTβR agonist combination therapy to monitor the real-time TLS/HEV development and dynamic tumor microenvironment in intravital microscopy (IVM). Transgenic mice with fluorescent red B cells and green fluorescent CD31+ blood vessels were infused with MECA-79 antibody (HEV marker) to visualize B cell trafficking through HEVs. Four-color confetti mice crossed with B cell-specific Cre mice, allowed us to analyze the clonal expansion of B cells expressing one of four colors, with daughter cells retaining their parent color. Our findings demonstrated that tumoral HEVs closely resemble those found in lymph nodes, characterized by fewer branches, longer segment lengths, and increased diameters compared to non-HEV tumor blood vessels, which typically exhibit chaotic patterns. Circulating B cells traveling through tumoral HEVs displayed significantly slower rolling velocities than non-HEV tumor vessels, likely due to enhanced integrin and L-selectin expression induced by the combination therapy. By repeated intravital imaging, we were also able to observe a quadruple increase in B cell number in TLS during the day 4-7 treatment time frame. Following adoptive transfer of splenic leukocytes from naïve donor mice, we found that these leukocytes preferentially homed to TLS-rich areas, with B cells constituting the majority of the recruited cells. Importantly, analyses using the confetti mouse model indicate that tumor infiltrating B cells underwent clonal expansion in TLS, with different TLS having different colors. Overall, our study demonstrates that HEVs are the gateways for B cell entry to tumors, and the intratumoral TLS formation is driven by localized clonal expansions of these B cells, resembling lymph node germinal center activities, which drive the development of humoral immunity against tumors. Citation Format: Gabrielle Rowe-Brown, Masanobu Komatsu. B cell infiltration and clonal expansion in tertiary lymphoid structures: Insights from intravital microscopy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr A010.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».