Tumour-infiltrating lymphocytes (TILs) are considered crucial in anti-tumour immunity. Accordingly, the presence of TILs contains prognostic and predictive value. In 2011, we performed a systematic review and meta-analysis on the prognostic value of TILs across cancer types. Since then, the advent of immune checkpoint blockade (ICB) has renewed interest in the analysis of TILs. In this review, we first describe how our understanding of the prognostic value of TIL has changed over the last decade. New insights on novel TIL subsets are discussed and give a broader view on the prognostic effect of TILs in cancer. Apart from prognostic value, evidence on the predictive significance of TILs in the immune therapy era are discussed, as well as new techniques, such as machine learning that strive to incorporate these predictive capacities within clinical trials.
Treatment of high grade serous ovarian cancer (HGSOC) after debulking and chemotherapy remains challenging. This phase 1 trial (NCT04739527) evaluates the use of a cell-based relapse vaccine, DCP-001, to prevent disease recurrence after primary treatment. Previous data in acute myeloid leukemia, has shown that DCP-001 induces an immune responses to tumor associated antigens, like WT1 and PRAME, frequently upregulated in HGSOC. In NCT04739527, DCP-001 is given four times biweekly (week 0, 2, 4 and 6) at a dose of 25 million cells/vaccination (vc), followed by 2 monthly boosters (week 14 and 18) of 10 million cells/vc, after primary debulking and chemotherapy. IFNγ ELISpot is performed on peripheral blood mononuclear cells after restimulation with WT1, PRAME, MAGEA3/4 and NY-ESO1. Vaccine induced T-cell response (VIR) at any point after week 0 are calculated as at least a 2-fold increase of the mock-corrected baseline response. Sustained VIR are counted if a VIR to the same antigen is observed in at least 2 timepoints after start of DCP-001. Flow cytometry is performed using a 40-marker panel to evaluate the immune profiles of innate and adaptive immune system, as well as activation and exhaustion markers and memory profiles. At present, a total of 7 patients have been included and 6 have completed the full vaccination schedule (week 22). DCP-001 is well-tolerated, with only mild to moderate adverse events, mainly related to local injection side reactions, or systemic discomfort with fatigue, diarrhea, temperature elevation and headache. Immune responses have been evaluated in 5 patients by IFNy ELISPOT. VIR were detected in a range of 0-8, and all but 1 patient had at least one sustained VIR to either of the 4 antigens. One patient had no VIR, however this patient had already high baseline responses to all 4 antigens. Flow cytometry showed changes during the vaccination in the immune profiles of these patients, with in general an activation of the innate and adaptive immune system. Detailed analysis is currently ongoing. Finally, at the week 22 visit, 2 patients had progressed during the treatment and 4 had no clinical signs of progressive disease. Taken together, initial data from the phase I trial demonstrate that DCP-001 is safe and well-tolerated and induces durable T-cell responses to tumor associated antigens in OC patients. The study will continue to enroll new patients, follow-up for progression and overall survival and will further analyze the immune responses induced by DCP-001. Citation Format: Marco De Bruyn, Annegé Vledder, Rob ten Pas, Anneke Eerkens, Koen Brummel, Hester van Zeeburg, Jeroen Rovers, Hans Nijman. Evaluation of immune response to tumor associated antigens in patients with high grade serous ovarian cancer vaccinated intra-dermally with DCP-001, an allogeneic, cancer cell-based vaccine. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4422.
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