Cancer immunotherapy response persists after lymph node resection

• DOI: 10.1101/2023.09.19.558262
• Publication Date: 2023-09-22T20:35:13Z
• Authors: Hengbo Zhou; Lutz Menzel; James W. Baish; Meghan J. O’Melia; Laurel B. Darragh; Derek N. Effiom; Emma Specht; Juliane Czapla; Pin-ji Lei; Johanna J. Rajotte; Lingshan Liu; Mohammad R. Nikma...; Mohammad S. Razavi; Matthew G. Vander...; Jessalyn M. Ubell...; Lance L. Munn; Sana D. Karam; Genevieve M. Boland; Sonia Cohen; Timothy P. Padera
• Keywords: Cancer Immunotherapy

ABSTRACT Surgical removal of lymph nodes (LNs) to prevent metastatic recurrence, including sentinel node biopsy (SLNB) and completion dissection (CLND), are performed in routine practice. However, it remains controversial whether removing LNs which critical for adaptive immune responses impairs checkpoint blockade (ICB) efficacy. Here, our retrospective analysis demonstrated that stage III melanoma patients retain robust response anti-PD1 inhibition after CLND. Using orthotopic murine mammary carcinoma models, we show ICB persist mice TDLN resection. Mechanistically, resection, antigen can be re-directed distant LNs, extends the responsiveness ICB. Strikingly, by evaluating head neck cancer treated neoadjuvant durvalumab irradiation, (metastases-free) remain reactive responders tumor disease-related LN hence, persistent anti-cancer reactions LNs. Additionally, delivered generated greater survival benefit, compared systemic administration. In complete responders, anti-tumor memory induced was rather than confined within lymphoid organs. Based on these findings, constructed a computational model predict free trafficking will undergo dissection.