Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma

Isazadeh, Alireza; Hajazimian, Saba; Garshasbi, Hamid; Shadman, Behrouz; Baghbanzadeh, Amir; Chavoshi, Reza; Taefehshokr, Sina; Jadid, Mahdieh Farhoudi Sefidan; Hajiasgharzadeh, Khalil

doi:10.1002/jcp.29905

Cited by 14 publications

(8 citation statements)

References 126 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[11][12][13] Cold tumors, such as prostate cancer and colon cancer, do not respond to single-agent ICB therapies because of their low immunogenicity. [13][14][15][16][17][18] Combination therapy has been used in the clinic to turn cold tumors into hot tumors in order to increase the efficacy of immunotherapy in recent years; such combination therapies include chemotherapy or radiation therapy combined with immunotherapy. 19 20 Chemotherapy and radiation can mainly lead to tumor cell apoptosis by disrupting cell division or destroying mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy

Wang

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundThe poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity.MethodsThe antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy.ResultsUSNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment.ConclusionThe administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.

show abstract

Section: Introductionmentioning

confidence: 99%

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy

Wang

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…Although the ORR has been increased by combined therapy independent of the PD-L1 level measured, not all patients benefit from the ICIs treatment, and this is termed a so-called primary resistance (30). Numerous studies have demonstrated the mechanisms of primary resistance in ICIs treatment (31)(32)(33), which include the absence of tumor-specific antigens, downregulation of antigen presentation molecules and suppression of T cell infiltration. Emerging evidence has indicated that bone and liver metastases might induce primary resistance to immunotherapy by regulating the immune microenvironment (23,24).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors

Yang

Cheng

et al. 2023

Oncol Lett

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment. In the present study, 143 patients with NSCLC receiving ICIs treatment were retrospectively analyzed. The objective response rate (ORR) was compared between the ALP high and low groups, bone metastasis and non-bone metastasis groups, and liver metastasis or non-liver metastasis groups. The associations between clinical characteristics, including ALP level, bone or liver metastasis and median progression-free survival (mPFS) time were analyzed by univariate and multivariate Cox regression analysis. It was found that bone metastasis was associated with a lower ORR (24 vs. 43%; P<0.05) and shorter mPFS (10.2 vs. 17.3 months; P=0.010) in patients with NSCLC receiving ICIs. Liver metastasis was associated with lower ORR (22 vs. 38%; P<0.05), but not with mPFS (P=0.119). The ALP level was higher in patients with bone or liver metastasis than in those without (119.6 or 103.6 vs. 83.3 U/l, respectively; P<0.05). Higher ALP levels were also associated with bone or liver metastasis, lower ORR (20 vs. 39%; P<0.05) and shorter mPFS (8.5 vs. 15.4 months; P=0.009). Cox regression analysis demonstrated that ALP was an independent prognostic indicator of mPFS (hazard ratio, 1.856; 95% confidence interval, 1.030-3.343; P=0.040). In conclusion, pretreatment levels of serum ALP might be a predictive indicator of clinical outcome in patients with NSCLC after ICIs treatment.

show abstract

“…In previous studies on cancer therapy, the use of anti-PD-1 and anti-PD-L1 mAbs has been seen as a significant milestone in managing cancer. This suggests that the inhibition of PD-1 and PDL-1 can be a highly effective strategy to reduce T-cell exhaustion, which, in turn, contains or manages various infectious diseases ( Figure 3 ) [ 149 , 166 ]. It is very well stated by Mohammed et al (2022) that the restoration of worn-out or exhausted T cells may be a successful tactic to combat COVID-19 [ 149 ].…”

Section: Immunomodulatory Approaches To Overcome T-cell Exhaustionmentioning

confidence: 99%

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines

et al. 2023

View full text Add to dashboard Cite

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells’ exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

show abstract

Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma

Cited by 14 publications

References 126 publications

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy

Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy

Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines

Contact Info

Product

Resources

About