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A randomized trial compared standard chemotherapy plus dostarlimab or placebo. Patients with mismatch repair–deficient tumors had 2-year progression-free survival of 61.4% with dostarlimab and 15.7% with placebo.

Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesterone (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2) and is associated with poor prognosis. Moreover, the systemic treatment options are limited. However, the TNBC is more likely than other breast cancer subtypes to benefit from immune checkpoint blockade therapy due to its higher immunogenicity, higher enrichment by tumour-infiltrating lymphocytes (TILs), and higher levels of programmed cell death ligand 1 (PD-L1) expression. Thus far, atezolizumab was approved in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic TNBC whose tumours express PD-L1. Currently, it seems that PD-L1-positive subgroup will potentially benefit the most from the immune checkpoint inhibitor (ICI) treatment. Moreover, it seems that better results are seen when an ICI is given as first-line treatment than when an ICI is given in later lines of treatment for advanced TNBC/metastatic TNBC. Recently, pembrolizumab has demonstrated promising results in early-stage TNBC what can lead in near future to its approval in (neo)adjuvant setting. This review summarizes the development and highlights recent advances of the atezolizumab and pembrolizumab in early and advanced/metastatic TNBC.

Previously untreated patients with advanced esophageal cancer were randomly assigned to receive chemotherapy alone, chemotherapy plus nivolumab, or nivolumab plus ipilimumab. Among patients with tumor-cell PD-L1 expression of 1% or greater, the two nivolumab regimens resulted in longer overall survival than chemotherapy. The side-effect profile was consistent with past reports on these agents.

Colorectal cancer (CRC) is the second most common cause of cancer mortality, with mismatch repair proficient (pMMR) and/or microsatellite stable (MSS) CRC making up more than 80% of metastatic CRC. Programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) immune checkpoint inhibitors (ICIs) are approved as monotherapy in many cancers including a subset of advanced or metastatic colorectal cancer (CRC) with deficiency in mismatch repair (dMMR) and/or high microsatellite instability (MSI-H). However, proficient mismatch repair and microsatellite stable (pMMR/MSS) cold CRCs have not shown clinical response to ICIs alone. To potentiate the anti-tumor response of PD-L1/PD-1 inhibitors in patients with MSS cold cancer, combination strategies currently being investigated include dual ICI, and PD-L1/PD-1 inhibitors in combination with chemotherapy, radiotherapy, vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors, mitogen-activated protein kinase (MEK) inhibitors, and signal transducer and activation of transcription 3 (STAT3) inhibitors. This paper will review the mechanisms of PD-1/PD-L1 ICI resistance in pMMR/MSS CRC and potential combination strategies to overcome this resistance, summarize the published clinical experience with different combination therapies, and make recommendations for future avenues of research.

Immune checkpoint inhibitors (ICIs) are effective for various types of cancer, and their application has led to paradigm shifts in cancer treatment. While many patients can obtain clinical benefits from ICI treatment, a large number of patients are primarily resistant to such treatment or acquire resistance after an initial response. Thus, elucidating the resistance mechanisms is warranted to improve the clinical outcomes of ICI treatment. ICIs exert their antitumor effects by activating T cells in the tumor microenvironment. There are various resistance mechanisms, such as insufficient antigen recognition by T cells, impaired T‐cell migration and/or infiltration, and reduced T‐cell cytotoxicity, most of which are related to the T‐cell activation process. Thus, we classify them into three main mechanisms: resistance mechanisms related to antigen recognition, T‐cell migration and/or infiltration, and effector functions of T cells. In this review, we summarize these mechanisms of resistance to ICIs related to the T‐cell activation process and progress in the development of novel therapies that can overcome resistance. While many patients can obtain clinical benefits from immune checkpoint inhibitor treatment, a large number of patients are primarily resistant to such treatment or acquire resistance after an initial response. There are various resistance mechanisms, and we classify them into three main mechanisms related to the T‐cell activation process: resistance mechanisms related to antigen recognition, T‐cell migration and/or infiltration, and effector functions of T cells.

Cancer immunotherapy has reached a critical point, now that immune checkpoint inhibitors and two CAR-T products have received market approval in treating 16 types of cancers and 1 tissue-agnostic cancer indication. Accompanying these advances, the 2018 Nobel Prize was awarded for the discovery of immune checkpoint pathways, which has led to the revolution of anti-cancer treatments. However, expanding the indications of immuno-oncology agents and overcoming treatment resistance face mounting challenges. Although combination immunotherapy is an obvious strategy to pursue, the fact that there have been more failures than successes in this effort has served as a wake-up call, placing emphasis on the importance of building a solid scientific foundation for the development of next-generation immuno-oncology (IO) agents. The 2019 China Cancer Immunotherapy Workshop was held to discuss the current challenges and opportunities in IO. At this conference, emerging concepts and strategies for IO development were proposed, focusing squarely on correcting the immunological defects in the tumor microenvironment. New targets such as Siglec-15 and new directions including neoantigens, cancer vaccines, oncolytic viruses, and cytokines were reviewed. Emerging immunotherapies were discussed in the areas of overcoming primary and secondary resistance to existing immune checkpoint inhibitors, activating effector cells, and targeting immunosuppressive mechanisms in the tumor microenvironment. In this article, we highlight old and new waves of IO therapy development, and provide perspectives on the latest momentum shifts in cancer immunotherapy.

Purpose Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. Methods We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were “hearing loss” OR “hearing impairment” OR “ototoxicity” OR “vestibular toxicity” OR “audiovestibular toxicity” AND “immune checkpoint inhibitor” OR “immunotherapy.” Results A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. Conclusion We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.

Microsatellite instability‐high (MSI‐H) is an important biomarker for predicting the effect of immune checkpoint inhibitors (ICIs) on advanced solid tumors. Microsatellite instability‐high is detected in various cancers, but its frequency varies by cancer type and stage. Therefore, precise frequency is required to plan ICI therapy. In this study, the results of MSI tests actually carried out in clinical practice were investigated. In total, 26 469 samples of various cancers were examined between December 2018 and November 2019 to determine whether programmed cell death‐1 blockade was indicated. The results of MSI tests were obtained for 26 237 (99.1%) of these samples. The male : female ratio was 51:49 and mean age was 64.3 years. In all samples, the overall frequency of MSI‐H was 3.72%. By gender, the frequency of MSI‐H was higher in female patients (4.75%) than in male patients (2.62%; P < .001). A comparison by age revealed that the frequency of MSI‐H was significantly higher in patients younger than 40 years of age (6.12%) and 80 years or older (5.77%) than in patients aged between 60 and 79 years (3.09%; P < .001). Microsatellite instability‐high was detected in 30 cancer types. Common cancer types were: endometrial cancer, 16.85%; small intestinal cancer, 8.63%; gastric cancer, 6.74%; duodenal cancer, 5.60%; and colorectal cancer, 3.78%. Microsatellite instability‐high was detected in cancer derived from a wide variety of organs. The frequency of MSI‐H varied by cancer type and onset age. These data should prove especially useful when considering ICI treatment. In this study, we presented real‐world data on microsatellite instability status in various unresectable or metastatic solid tumors to determine if pembrolizumab treatment was indicated.

Adjuvant chemotherapy has not improved disease-free survival among patients with resected esophageal or gastroesophageal junction cancer. In this trial, after neoadjuvant chemoradiotherapy and resection, patients with residual disease were randomly assigned to receive nivolumab or placebo. Nivolumab doubled the median disease-free survival from 11.0 to 22.4 months.

The increasing use of immune checkpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immune checkpoint inhibitors, mainly activated T‐cells, can attack normal tissues and organs in the body and lead to a variety of adverse effects. In the lung, these attacks can induce checkpoint inhibitor pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and has the potential to be fatal if not treated correctly. In this review, we summarize the characteristics of CIP and provide advice on how to manage this disease.