Neoadjuvant immunotherapy in gastrointestinal cancers – The new standard of care?

• Published in: Seminars in cancer biology Vol. 86; pp. 834 - 850
• Main Authors: Petricevic, Branka, Kabiljo, Julijan, Zirnbauer, Rebecca, Walczak, Henning, Laengle, Johannes, Bergmann, Michael
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2022
• Subjects: Gastrointestinal; GI cancer; ICI; Immune checkpoint inhibitors; Immunotherapy; Neoadjuvant; MSI-L; FOLFIRINOX; GI NET; CLM; FLOT; Gastrointestinal; GI cancer; SASP; DFS; Gy; GM-CSF; DOC; TNT; PFS; TNBC; AC; IL; EAC; i.p; Immune checkpoint inhibitors; GEJ; BTC; i.v; RC; PDAC; POT; HNSCC; MIS; VSV; IAV; FDA; RT; IMRT; NMIBC; LARC; DAMPs; HPV; GEMOX; cGAS; PD-L1; TAAs; INMC; CB; CC; CD; NDV; MSI; NSCLC; SOC; TREX1; MKI; ICD; MSS; ChT; ICI; eCCA; STING; CALR; 5-FU; ALK; TAM; LN; CPS; ITT; W&W; HMGB1; mFOLFOX6; IDO; Immunotherapy; MG; FOLFOX4; Th17; EC; RWD; RFS; BATF3; HSP; TACE; HCC; MV; SIRPα; s.c; HSV; VEGF-A; AVC; ESCC; CRC; NK; PD-1; TLR4; vs; MoA; VV; CRT; COX-2; Neoadjuvant; EGFR; IFN; dCCA; EFS; GBM; S1P; CAPOX; DCs; LAG-3; PTX; pCCA/Klatskin; CTLA-4; TIM-3; pCR; GI; GIST; OS; OV; Treg; iCCA; TMB; TIME; SCPRT; APC; SBRT; MIBC; irAEs; gastrointestinal; neoadjuvant; immune checkpoint inhibitors; immunotherapy
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2022.05.015

The development of immune checkpoint inhibitors (ICI) offers novel treatment possibilities for solid cancers, with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the metastatic and adjuvant setting for select cancers, such as melanoma, non-small cell lung cancer (NSCLC) or urological malignancies. Currently, there is ample clinical interest in employing ICI in a neoadjuvant setting with a curative intent. This approach is especially supported by the scientific rationale that ICI primarily stimulate the host immune system to eradicate tumor cells, rather than being inherently cytotoxic. Aside from tumor downstaging, neoadjuvant immunotherapy offers the potential of an in situ cancer vaccination, leading to a systemic adjuvant immunological effect after tumor resection. Moreover, preclinical data clearly demonstrate a synergistic effect of ICI with radiotherapy (RT), chemoradiotherapy (CRT) or chemotherapy (ChT). This review harmonizes preclinical concepts with real world data (RWD) in the field of neoadjuvant ICI in gastrointestinal (GI) cancers and discusses their limitations. We believe this is a crucial approach, since up to now, neoadjuvant strategies have been primarily developed by clinicians, whereas the advances in immunotherapy primarily originate from preclinical research. Currently there is limited published data on neoadjuvant ICI in GI cancers, even though neoadjuvant treatments including RT, CRT or ChT are frequently employed in locally advanced/oligometastatic GI cancers (i.e. rectal, pancreatic, esophagus, stomach, etc.). Utilizing established therapies in combination with ICI provides an abundance of opportunities for innovative treatment regimens to further improve survival rates.