The gut microbiome has emerged as a critical factor influencing the efficacy of cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs). Recent studies have highlighted the potential of using the ecological topology of gut microbiota as a biomarker for predicting patient responses to ICIs. Derosa et al. developed a scoring system, termed TOPOSCORE, which integrates the quantification of Akkermansia species to assess the microbiome's ecological structure. This scoring method was validated in a cohort of 254 non-small cell lung cancer (NSCLC) patients and 216 genitourinary cancer patients, demonstrating its predictive power for immunotherapy outcomes (ref: Derosa doi.org/10.1016/j.cell.2024.05.029/). Additionally, Ning et al. emphasized the heterogeneity of previous studies on gut microbiome biomarkers, suggesting that the ecological topology approach could standardize predictions of immunotherapy efficacy (ref: Ning doi.org/10.1016/j.cell.2024.04.044/). Together, these findings underscore the gut microbiome's role as a next-generation biomarker in cancer immunotherapy, paving the way for personalized treatment strategies based on microbiome profiling.

Neoadjuvant immunotherapy has shown promising results in various cancer types, particularly in resectable melanoma and mismatch repair-deficient colon cancer. In a study by Blank et al., patients with resectable stage III melanoma receiving neoadjuvant nivolumab and ipilimumab exhibited impressive 12-month recurrence-free survival rates of 95.1% for those with a major pathological response, compared to 57.0% for nonresponders (ref: Blank doi.org/10.1056/NEJMoa2402604/). Similarly, Chalabi et al. reported that neoadjuvant nivolumab plus ipilimumab in locally advanced dMMR colon cancer resulted in a high pathological response rate, indicating a favorable safety profile and potential for improved outcomes (ref: Chalabi doi.org/10.1056/NEJMoa2400634/). Zhou et al. expanded on this by investigating neoadjuvant SHR-1701 in unresectable stage III NSCLC, achieving a post-induction objective response rate of 58% and an 18-month event-free survival rate of 56.6% (ref: Zhou doi.org/10.1016/j.ccell.2024.05.024/). These studies collectively highlight the efficacy of neoadjuvant immunotherapy in enhancing surgical outcomes and long-term survival across different cancer types.

Chimeric antigen receptor (CAR) therapy has evolved significantly, with recent studies exploring its application in various malignancies. Peng et al. conducted in vivo AAV-SB-CRISPR screens on tumor-infiltrating NK cells, identifying CALHM2 as a genetic checkpoint that enhances cytotoxicity and tumor infiltration when knocked out (ref: Peng doi.org/10.1038/s41587-024-02282-4/). This finding suggests that genetic modifications can improve the efficacy of CAR-NK cell therapies. In gastrointestinal cancers, Qi et al. reported final results from a phase 1 trial of satri-cel, a CAR T cell targeting CLDN18.2, demonstrating promising safety and efficacy in patients with advanced disease (ref: Qi doi.org/10.1038/s41591-024-03037-z/). Furthermore, Morschhauser et al. presented results from the TRANSCEND FL study, which evaluated lisocabtagene maraleucel in follicular lymphoma, achieving significant overall response rates (ref: Morschhauser doi.org/10.1038/s41591-024-02986-9/). These studies illustrate the expanding landscape of CAR therapies, highlighting their potential in treating various cancers while addressing the challenges of immune evasion and tumor heterogeneity.

The tumor microenvironment (TME) plays a pivotal role in cancer progression and immune evasion. Tharp et al. demonstrated that tumor-associated macrophages (TAMs) contribute to a fibrotic TME that restricts CD8+ T cell infiltration, thereby promoting tumor growth (ref: Tharp doi.org/10.1038/s43018-024-00775-4/). This finding underscores the importance of targeting TAMs to enhance antitumor immunity. Chang et al. developed the LORIS score, which predicts patient outcomes following immune checkpoint blockade therapy by analyzing clinical, pathologic, and genomic features from a large dataset (ref: Chang doi.org/10.1038/s43018-024-00772-7/). Additionally, Jiang et al. explored the metabolic interactions between macrophages and fibroblasts in gastric cancer, revealing a dual prognostic significance of nicotinamide metabolism that influences the TME and immune response (ref: Jiang doi.org/10.1016/j.cmet.2024.05.013/). These studies collectively highlight the complex interplay within the TME and its impact on therapeutic efficacy, suggesting that strategies targeting the TME could enhance the effectiveness of immunotherapies.

Checkpoint inhibitor therapy has revolutionized cancer treatment, with recent studies providing insights into its long-term efficacy and potential biomarkers. Melero et al. presented 5-year results from the CheckMate 040 study, demonstrating that nivolumab plus ipilimumab remains effective in patients with advanced hepatocellular carcinoma previously treated with sorafenib, with durable responses observed (ref: Melero doi.org/10.1016/j.annonc.2024.03.005/). In the KEYNOTE-361 trial, Powles et al. investigated the role of circulating tumor DNA (ctDNA) as a biomarker in advanced urothelial carcinoma, although the study did not meet its efficacy thresholds (ref: Powles doi.org/10.1038/s41591-024-03091-7/). Shi et al. evaluated finotonlimab combined with chemotherapy in recurrent head and neck cancer, finding significant overall survival benefits (ref: Shi doi.org/10.1038/s41591-024-03110-7/). These findings emphasize the importance of identifying reliable biomarkers for predicting responses to checkpoint inhibitors and highlight the ongoing need for combination strategies to enhance treatment outcomes.

Proteogenomics has emerged as a powerful approach to identify novel therapeutic targets across various cancer types. Savage et al. conducted a pan-cancer analysis integrating proteogenomic data from 1,043 patients, revealing a wealth of druggable proteins and biological factors influencing mRNA-protein correlation (ref: Savage doi.org/10.1016/j.cell.2024.05.039/). This comprehensive analysis expands the landscape of potential therapeutic targets, highlighting the need for further exploration in clinical settings. Ramberger et al. focused on multiple myeloma, revealing insights into disease biology and therapeutic opportunities through a systematic assessment of the proteome (ref: Ramberger doi.org/10.1038/s43018-024-00784-3/). Together, these studies underscore the significance of proteogenomics in advancing our understanding of cancer biology and identifying new avenues for targeted therapies.

Combination therapies are increasingly recognized for their potential to enhance treatment efficacy in cancer. Lao et al. investigated the role of glutaryl-CoA dehydrogenase (GCDH) in hepatocellular carcinoma, demonstrating that GCDH suppresses tumor progression through metabolic reprogramming, which could synergize with other therapeutic modalities (ref: Lao doi.org/10.1016/j.jhep.2024.05.034/). Zhang et al. explored the use of biodegradable scaffolds to enhance the antitumor activity of CAR-T cells, showing that these scaffolds can improve T cell proliferation and cytotoxicity by mimicking physiological activation conditions (ref: Zhang doi.org/10.1038/s41551-024-01216-4/). Zanwar et al. examined the impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel, revealing significant differences in response rates and survival based on the presence of extramedullary disease (ref: Zanwar doi.org/10.1186/s13045-024-01555-4/). These findings highlight the importance of combination strategies in overcoming therapeutic resistance and improving patient outcomes.

Emerging biomarkers and innovative therapeutic strategies are crucial for advancing cancer treatment. Villa et al. investigated the role of TREM2 in glioblastoma-associated myeloid cells, revealing its dual function in promoting inflammation and suppressing immune responses depending on the microenvironment (ref: Villa doi.org/10.1016/j.ccell.2024.05.018/). This research opens new avenues for neuro-oncological immunotherapy by targeting myeloid cell functions. Yao et al. introduced hybrid membrane-camouflaged immunomodulatory nanoturrets designed for sequential drug release, enhancing T cell-mediated anticancer immunity (ref: Yao doi.org/10.1021/jacs.4c04840/). These studies emphasize the need for innovative approaches to reverse immunosuppressive tumor microenvironments and improve the effectiveness of immunotherapies, highlighting the potential for novel biomarker-driven strategies in personalized cancer treatment.