Core Viewpoint - The article discusses the promising results of fecal microbiota transplantation (FMT) combined with immunotherapy in treating non-small cell lung cancer (NSCLC), melanoma, and metastatic renal cell carcinoma (mRCC), highlighting its potential to overcome resistance to PD-1 therapy and improve patient outcomes [2][3][4]. Group 1: FMT and Immunotherapy in NSCLC and Melanoma - The FMT-LUMINate trial demonstrated an objective response rate (ORR) of 80% (16/20) in NSCLC and 75% (15/20) in melanoma, achieving the primary endpoint [8]. - Safety assessments indicated no grade 3 or higher adverse events in the NSCLC cohort, while 65% of melanoma patients experienced grade 3 or higher adverse events [8]. - The study found that responders had a unique gut microbiome composition post-FMT, with significant reductions in specific bacterial species associated with non-responders [9]. Group 2: FMT in Metastatic Renal Cell Carcinoma - The PERFORM trial showed that 50% (10/20) of mRCC patients experienced grade 3 immune-related adverse events, with no severe FMT-related toxicities reported [11][14]. - The objective response rate was 50% (9/18), including 11% (2/18) achieving complete response, with most responders not experiencing severe immune-related adverse events [14]. - Improvements in gut microbiome diversity were linked to reduced toxicity and enhanced treatment response, while the presence of specific bacteria correlated with higher immune-related adverse events [15][16]. Group 3: FMT Combined with Pembrolizumab and Axitinib - The TACITO trial evaluated the efficacy of donor-derived FMT in mRCC patients receiving pembrolizumab and axitinib, with a primary endpoint of disease progression-free survival [18][21]. - Although the primary endpoint was not met, the donor FMT group showed a significantly longer median progression-free survival of 24.0 months compared to 9.0 months in the placebo group [22]. - The donor FMT group had an ORR of 52%, while the placebo group had 32%, indicating potential benefits of selective donor FMT in enhancing immunotherapy outcomes [22].

Core Viewpoint - The personalized neoantigen vaccine developed by Dana-Farber Cancer Institute shows significant potential in inducing strong immunity in melanoma patients, although its immunogenicity still requires enhancement [1][2]. Group 1 - The study published in the journal Cell highlights the development of a multi-adjuvant personalized neoantigen vaccine that effectively stimulates immunity in melanoma patients [1][2]. - The research involved testing a long peptide vaccine on 10 melanoma patients, utilizing two adjuvants, Montanide and poly-ICLC, in conjunction with local injection of Ipilimumab and systemic use of Nivolumab [4]. - Among the 9 patients who completed vaccination, the personalized vaccines induced ex vivo T cell responses targeting most neoantigens, with 6 patients generating ex vivo CD8+ T cell responses [5]. Group 2 - Key findings of the study include the ability of most neoantigens to induce ex vivo T cell responses, including CD8+ cell responses [8]. - The vaccine induced dynamic changes in myeloid cell populations at the injection site [8]. - The neoantigen vaccination reshaped the T cell receptor repertoire specific to tumors beyond anti-PD-1 treatment, revealing vaccine-specific tumor-infiltrating lymphocytes (TIL) through TCR reconstruction and antigen screening [8].