Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma:A case report

BACKGROUND Immune checkpoint inhibitors,including programmed death-ligand 1(PD-L1)and programmed death-1(PD-1)have recently been approved to treat locally advanced and metastatic urothelial carcinoma(UC).However,some patients experience rapid tumor progression rather than any clinical benefit from anti-PDL1/PD-1 therapy.CASE SUMMARY A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo.The patient could not tolerate further chemotherapy.Next-generation sequencing was performed,and the results indicated that the tumor mutational burden was 6.4 mutations/Mb.The patient received the anti-PD-L1 agent toripalimab combined with albuminbound paclitaxel.Compared with the baseline staging before immunotherapy,the patient had a treatment failure time of<2 mo,an increase in tumor burden of>50%,and a>2-fold increase in progression,indicating hyperprogression.CONCLUSION Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging.For older patients with advanced UC who have already exhausted multi-line chemotherapy options,immunotherapy should be used prudently if no effective biomarker is available.Further studies are required to clarify the causes and mechanisms of hyperprogression.

Hyperprogression under treatment with immune-checkpoint inhibitors in patients with gastrointestinal cancer:A natural process of advanced tumor progression?

Immunotherapy has shown great promise in treating various types of malignant tumors.However,some patients with gastrointestinal cancer have been known to experience rapid disease progression after treatment,a situation referred to as hyperprogressive disease(HPD).This minireview focuses on the definitions and potential mechanisms of HPD,natural disease progression in gastrointestinal malignancies,and tumor immunological microenvironment.

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

In 2017,immune response evaluation criteria in solid tumors(iRECIST)were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy,considering the different time of following and response,between this new therapy compared to the standard one.However,even if the iRECIST are worldwide accepted,to date,different aspects should be better underlined and well reported,especially in clinical practice.Clinical experience has demonstrated that in a non-negligible percentage of patients,it is challenging to determine the correct category of response(stable disease,progression disease,partial or complete response),and consequently,to define which is the best management for those patients.Approaching radiological response in patients who underwent immunotherapy,a new uncommon kind of target lesions behavior was found.This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug.Therefore,new groups of response have been described in clinical practice,defined as“atypical responses,”and categorized into three new groups:pseudoprogression,hyperprogression,and dissociated response.This review summarizes and reports these patterns,helping clinicians and radiologists get used to atypical responses,in order to identify patients that respond best to treatment.

Advancing to the era of cancer immunotherapy

Cancer greatly affects the quality of life of humans worldwide and the number of patients suffering from it is continuously increasing.Over the last century,numerous treatments have been developed to improve the survival of cancer patients but substantial progress still needs to be made before cancer can be truly cured.In recent years,antitumor immunity has become the most debated topic in cancer research and the booming development of immunotherapy has led to a new epoch in cancer therapy.In this review,we describe the relationships between tumors and the immune system,and the rise of immunotherapy.Then,we summarize the characteristics of tumor-associated immunity and immunotherapeutic strategies with various molecular mechanisms by showing the typical immune molecules whose antibodies are broadly used in the clinic and those that are still under investigation.We also discuss important elements from individual cells to the whole human body,including cellular mutations and modulation,metabolic reprogramming,the microbiome,and the immune contexture.In addition,we also present new observations and technical advancements of both diagnostic and therapeutic methods aimed at cancer immunotherapy.Lastly,we discuss the controversies and challenges that negatively impact patient outcomes.

Paradox-driven adventures in the development of cancer immunology and immunotherapy

After more than one hundred years of documented trials,immunotherapy has become a standard of care in the treatment of human cancer.Much of the knowledge that led to recent breakthroughs seems quite logical from today’s point of view.However,what we now cite as facts were originally considered paradoxes,meaning something contrary to expectations or perceived opinion at the time.In order to make gains in the field of immunotherapy,one had to be willing to confront ideas and concepts that seemed to contradict one another,and reconcile how each could be true.This is what led to new knowledge and advances.Here,we highlight some of these paradoxes and the milestone discoveries that followed,each one critical for our understanding of immune checkpoint pathways.By outlining some of the steps that we took and the challenges that we overcame,we hope to inspire and encourage future generations of researchers to confront the paradoxes that still permeate the field.