Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells

Abstract

The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens.

Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy

“…To refine the definition of the pan-cancer-associated gut dysbiosis ("GOMS") discussed above, we propose herein the following meta-analysis (GLOSSARY). We performed microbiome taxonomic profiling with MetaPhlAn 4 34 on stool samples collected from adult individuals from a first collection of 1,879 patients spanning 8 different cancers comprising 30 cohorts from 23 published studies [22][23][24][25][26][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] and 5,341 control individuals comprising 17 cohorts of healthy adult subjects from 14 published studies across diverse geographic locations 45,[53][54][55][56][57][58][59][60][61][62][63][64][65] (Table S2, refer to supplemental materials for meta-analysis methodology). With the exception of colorectal cancer, the cancer datasets typically contained only cancer patients as they are focused on studying response to treatment and matched controls individuals are difficult to be collected in oncological settings.…”

High-resolution transcriptomics analysis of CXCL13+ EPSTI1+ CDK1+ cells with a specific focus on lung adenocarcinoma

“…Similarly, therapies have been shown to result in a decrease in proliferating T cells in hepatocellular carcinoma ( 41 ). Proliferating T cells being in a state of memory but not in exhaustion may contribute to long-term responses ( 42 ). It is of interest to further investigate of the transition from memory to exhaustion.…”

Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation

“…Upregulated expression and enhanced presentation of TAAs after RT result in potent cancer vaccination, and TSAs originated from RT-induced or somatic nonsynonymous mutations may not easily develop immune tolerance and can be further utilized to develop neoantigen-based peptide cancer vaccines. 51 Specifically, four gene mutations (Adgrf5, Cand1, Dhx58, and Raet1e) upregulated by RT (8 Gy × 3 fractions) and their encoded immunogenic neoepitopes in 4T1 cells were recently identified. 52 In addition, it was reported that immunogenic mutation in a gene, KPNA2, upon radiation-induced exposure occurred in a lung cancer patient after surgical removal of two brain metastases.…”