Immunotherapy最新文献

Chronic spontaneous urticaria (CSU) is a complex inflammatory skin condition that significantly impacts patients' quality of life. Conventional treatments, such as antihistamines, often fail to provide adequate symptom control. The next step involves administering omalizumab, a monoclonal antibody targeting IgE, however, a subset of patients may not respond to this treatment underscoring the necessity for alternative treatment options. Remibrutinib, an oral, selective inhibitor of Bruton's tyrosine kinase (BTK), has emerged as a promising therapy in CSU. BTK is vital for the activation of mast cells and basophils. The inhibitory action of remibrutinib on BTK may help alleviate CSU symptoms by addressing mast cell-mediated inflammation. Clinical trials, including Phase II and III studies, have shown promising efficacy and a favorable safety profile for remibrutinib in treating CSU. Patients experienced rapid symptom relief, with notable improvements in the Urticaria Activity Score (UAS7) concerning both itch intensity and the severity of hives. The safety profile was also commendable, with no significant treatment-related adverse events requiring therapy cessation or posing immediate health risks to patients. These results indicate that remibrutinib may become a preferred oral treatment for patients with moderate to severe CSU who do not adequately respond to standard therapies.

Immunotherapy has become a significant research focus for cancer treatment in recent years because it can generate enduring immunological responses and has promising therapeutic potential. Nevertheless, excessive stimulation of the immune system may adversely affect healthy organs, which can lead to immune-related toxicities, including gastrointestinal, pulmonary, hepatic, and dermatological toxicities. Among them, gastrointestinal toxicity induced by the immune response is the most common. Immune-associated enteritis has an incidence rate of 8%-27% and is one of the most prevalent forms of gastrointestinal toxicity. Tislelizumab is an approved first-line treatment for individuals with recurrent or metastatic nasopharyngeal cancer functioning as an inhibitor of PD-1. Here, we report a patient with nasopharyngeal carcinoma who developed bloody stools and diarrhea after two cycles of tislelizumab. Abdominal CT revealed intestinal wall thickening with inflammatory exudation. Congestion, edema, and mucosal punctate ulcers were discovered during the colonoscopy. Histopathology confirmed active mucosal inflammation. The initial treatment with loperamide, bifidobacterium tetrad, and norfloxacin failed, but the symptoms improved significantly after switching to metronidazole, mesalazine, and methylprednisolone. This article reviewed a case of immunological enteritis triggered by tislelizumab, demonstrating that mesalazine can markedly alleviate the symptoms of immune-associated enteritis, aiming to enhance future clinical efforts regarding tislelizumab-induced immunological enteritis.

Aim: To evaluate whether immune checkpoint inhibitor (ICI) therapy is associated with a higher incidence of hypertension (HTN) among cancer patients compared to those not treated with ICIs.

Materials & methods: This retrospective cohort study utilized data from the TriNetX Research Network, a global database of de-identified electronic health records. Adult patients (≥18 years) with lung, breast, colon, kidney, or skin cancer were categorized based on ICI treatment. Patients with preexisting hypertension were excluded. Propensity score matching (1:1) based on demographics and comorbidities yielded two balanced cohorts of 24,956 patients each. The primary outcome was the incidence of hypertension within one year of cancer diagnosis.

Results: The incidence of hypertension was significantly higher in the ICI group (13.2%) compared to the non-ICI group (9.7%). The risk ratio was 1.356 (95% CI: 1.271-1.446), and the odds ratio was 1.410 (95% CI: 1.311-1.516), both with p < 0.001. Kaplan-Meier analysis showed lower hypertension-free survival in the ICI group (log-rank p < 0.001; HR = 1.071).

Conclusions: ICI therapy is significantly associated with an increased risk of developing hypertension. These findings support the need for routine cardiovascular monitoring in patients receiving ICI treatment.

Aims: To determine whether using a pH-sensitive peptide (CBX-15) for antigen-independent targeting of MMAE to tumors induced anti-tumor efficacy via direct and immunological mechanisms in the rat tumor model.

Methods: CBX-15 was assessed for its ability to kill tumor cells and induce immunogenic cell death (ICD) in female Fischer rats bearing syngeneic 13762 mammary adenocarcinoma tumors via in vivo and ex vivo functional assays.

Results: CBX-15 demonstrated efficacy, safety and anti-tumor immunologic memory, demonstrated by the ability of both CBX-15-cured and vaccinated rats to reject further tumor challenge. Responding rats exhibited the induction of ICD-induced immunomodulatory activity, including recognition of tumor cells ex vivo, recruitment of TILs and increases in memory CD4⁺ T lymphocytes in the bone marrow.

Conclusion: CBX-15 eradicates tumors by a combination of both direct cytotoxic action of MMAE as well as through the induction of ICD, the latter of which results in long term anti-tumor immunological memory. To our knowledge, this is the first work demonstrating both anti-tumor efficacy and induction of long-term anti-tumor immune memory by a tumor-selective drug in the rat, the species used for preclinical toxicological evaluation. This study provides a strong justification for exploring combination therapies with CBX-15 and other immunomodulators.

Immunotherapy for gastrointestinal cancers has elicited considerable amount of attention as a viable therapeutic option for several cancer types. Gut microbiome as a whole plays a critical role in shaping immune responses and influencing cancer progression. Recent evidence suggests that Helicobacter pylori (H. pylori), may influence immunotherapy efficacy by modulating the tumor microenvironment. Infection with H. pylori is common as it affects approximately 50% of the global population and remains the leading risk factor for gastric cancer. Interestingly, recent clinical and preclinical data has associated H. pylori with colorectal cancer carcinogenesis. Gut microbiome appears to be a modulator of the relationship between the immune system, gastrointestinal cancer development and existing therapies. Infection with H. pylori may affect immunotherapy results in both gastroesophageal and colorectal cancer; favorable results were noticed in H. pylori positive patients with gastric cancer, while in colorectal cancer patients the pathogen seemed to impede immunotherapy's action. This article aims to review current data on the role of H. pylori in triggering gastric inflammation and cancer, as well as its potential involvement in colorectal cancer development. Additionally, it seeks to highlight the impact of H. pylori infection on the response to immunotherapy in gastrointestinal cancers.

Background: Although immune checkpoint inhibitors (ICIs) are widely used for patients with cancer, evidence of the impact of ICIs on the incidence of arthralgia remains limited.

Objective: To evaluate the impact of ICIs on arthralgia incidences in patients with cancer.

Methods: We performed a systematic review to identify phase 3 randomized control trials (RCTs) evaluating ICIs in patients with cancer and reporting the incidence of arthralgia. We performed a meta-analysis to pool odds ratios (ORs) of any grade and grade 3-5 arthralgia.

Results: Forty RCTs (n = 26,610) were included. The incidence of any-grade and grade 3-5 treatment-related arthralgia was 12.0% (n = 1,125/9,395) and 0.54% (n = 47/8,723). The addition of an ICI to systemic therapy, such as chemotherapy, significantly increased any-grade (OR 1.32, 95% CI: 1.13-1.54, p = 0.001) and grade 3-5 arthralgia (OR 1.78, 95% CI: 1.08-2.94, p = 0.02) with low heterogeneity among ICI subtype subgroups (I² = 0%). ICI monotherapy was associated with higher incidences of arthralgia than non-taxane (OR 6.83, 95% CI: 3.05-15.30, p < 0.001) but not than taxane chemotherapy (OR 0.74, 95% CI: 0.44-1.24, p = 0.25).

Conclusions: These results could guide oncologists to assess arthralgia in patients receiving ICIs.

Immune-related adverse events typically occur during the early phases of immune checkpoint inhibitor therapy. However, late-onset immune-related adverse events can still arise long after the immune checkpoint inhibitor therapy has ended. Immune checkpoint inhibitor-related pneumonitis warrants special attention for risk assessment and early detection due to its potential for serious outcomes, including hospitalization and death. Despite its rarity, late-onset immune checkpoint inhibitor-related pneumonitis should be considered in the differential diagnosis for dyspnea in patients with a history of immune checkpoint inhibitor therapy to prevent morbidity and mortality. In this case report, we present a case of an 84-year-old female patient suffering from locally advanced triple-negative breast cancer and late-onset immune checkpoint inhibitor-related pneumonitis requiring hospitalization 104 days after the last cycle of pembrolizumab. Following successful treatment of late-onset immune checkpoint inhibitor-related pneumonitis with corticosteroids, a recurrence of immune checkpoint inhibitor-related pneumonitis occurred a month later. Corticosteroid therapy was reinitiated, gradually tapered after radiological improvement, and eventually discontinued. The patient remains in remission from breast cancer. For patients with a history of immune checkpoint inhibitor therapy, medical vigilance, accurate diagnosis, and timely management of late-onset immune checkpoint inhibitor-related pneumonitis are crucial.

Liquid biopsy is a laboratory test used to detect and analyze circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and other tumor-derived components, in a blood sample. In the context of breast cancer (BC), liquid biopsies hold significant promise for guiding the use of immune checkpoint inhibitors and immune-based combinations, offering real-time insights into tumor dynamics, treatment response, and resistance mechanisms. This review explores the role of liquid biopsy in BC immunotherapy, focusing on its applications, benefits, issues, and current and future research directions.