Enhanced Germinal Center Reactions Within Tertiary Lymphoid Structures Following Neoadjuvant Chemotherapy and Intestinal Care-A Path to Robust Antitumor Immune Response in Borderline Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: In 2019, 4 patients with borderline resectable-pancreatic ductal adenocarcinoma(BR-PDAC)received neoadjuvant chemotherapy(NAC)with 3 cycles of gemcitabine plus nab-paclitaxel(GnP)over 12 weeks in combination with intestinal care, and subsequently underwent pancreatectomy. Surprisingly, histological response to NAC was Grade 3(viable tumor cells <10%)in 3 out of 4 patients. Aim/subjects: This study aimed to clarify the histopathological findings common to 3 patients with Grade 3 histological response to NAC. RESULTS: Common histopathological findings were as follows: 1)each tumor bed was extensively replaced by fibrous connective tissues with a high degree of inflammatory cell infiltration, and almost no viable cancer cells were observed; 2)all cancer cells within the perineural space where perineural invasion is usually seen, had undergone cytolysis; 3)tertiary lymphoid structures(TLSs)with germinal centers were found at the periphery of each tumor bed, and many plasma cells were seen adjacent to TLSs; and 4)a lot of tingible body macrophages that phagocytosed apoptotic B cells were present around germinal center. CONCLUSIONS: NAC with 3 cycles of GnP over 12 weeks in combination with intestinal care elicited a potent antitumor immune response through enhanced germinal center reactions within TLSs.