Major Changes in Cancer Treatment: A Decade of Immune Checkpoint Inhibitors.

Caroline Robert, from the Gustav Rousey Institute and the University of Paris-Sakre, recently published a review in the journal Nature Communications entitled "A decade of immune-checkpoint resedors in the cancerrapy" commenting on the development of immuno-checkpoint inhibitors in cancer treatment over the past decade.
the revival of cancer immunotherapy over the past decade, the most important achievement in cancer treatment has undoubtedly been the introduction of immunomodulants targeting T-cells to block immunoassociative checkpoints CTLA-4 and PD-1 or PDL-1.
2011, ipilimumab, the first antibody to block the immune checkpoint (CTLA4), was approved.
then quickly developed monoclonal antibodies against PD-1 and PDL-1.
anti-PD-1 / PDL-1 antibodies have become the most widely prescribed anti-cancer therapies.
now, T-cell-targeted immunomodulants can be used as a single drug or in combination with chemotherapy as a first- or second-line treatment for about 50 types of cancer.
there are currently more than 3,000 effective clinical trials evaluating T-cell regulators, accounting for about two-thirds of all oncology trials.
, however, a decade ago, just before the era of immunosuppressants (ICI), solid tumor immunotherapy was in a critical situation.
therapy was based mainly on immunocytokines, such as lecierle mesokine 2 or alpha-interferon, which were ineffective and highly toxic.
trials have tested many forms of cancer vaccines, most of which are ineffective.
However, after the first success of ICI immunotherapy, to this day, the situation has reversed, immunotherapy has taken the lead in this field, immunologists have regained significant influence in cancer research, and the winners of the 2018 Nobel Prize in Medicine are two immunologists who are based on ICI immunotherapy The originers, James Allison and Tasuku Honjo, have no doubt that this cancer treatment honor is well deserved because ICI has made tremendous clinical progress in treating certain invasive cancers, such as metastasis melanoma, and is the first disease to prove ICI's efficacy.
ICI immunotherapy not only has significant efficacy in some patients, but also revolutionizes the field of oncology in many ways.
changed the way doctors assess the effectiveness of treatment or deal with adverse events.
it also provides a more comprehensive perspective on cancer patients, not just cancer cells, but also creates new and productive interactions between immunologists, oncologists and other organ specialists.
, the success of immunotherapy depends on destroying cancer by activating the host immune system, giving people a more comprehensive understanding of the cancer.
now takes into account not only the cancer cells that are being targeted and destroyed, but also the cancer immune environment.
now, people are fully aware that preclinical testing of conventional cancer drugs on cultured cancer cell line and immunodeficiency animals is of little significance.
now, new, more reliable preclinical models using immune-functioning animals are being used more widely.
currently, new tools for transformational and clinical research include immune parameters such as the presence and activation status of tumor-immersed T-cells, expression of Immune checkpoint PDL-1, or assessment of tumor mutation burden (TMB).
, on the other hand, in ICI immunotherapy, the possibility of multiple new antigens from highly mutant tumors appears to be a favorable response factor.
this is why lung cancer patients who smoke respond better to immunotherapy than non-smokers.
the correlation between high TMB and immunotherapy response, anti-PD-1 drugs are licensed for highly mutated cancers associated with misalacted DNA repair defects (microsatelliter instability).
is a rare example in the history of cancer treatment, where drugs are licensed based on bio-oncology mechanisms, regardless of the type of tumor.
even after the initial increase in the size of the metastasis, ICI immunotherapy can induce delayed tumor responses.
may be due to delayed efficacy of immunotherapy, or to a brief increase in tumor size due to the initial collection of immune cells.
, the Standard Radiological Evaluation Standard (RECIST-1.1), commonly used to monitor chemotherapy or targeted therapeutic reactions, does not apply to these new reaction dynamics.
, the iRECIST (Immune Recirculation) assessment system incorporates new evaluation criteria guidelines, including longer time to identify or negate tumor increases.
other significant change in the disease is related to adverse events associated with immunotherapy, which are completely different from previous treatments, cytotoxicity or targeted therapies.
because ICI mechanisms rely on physiological brakes that inhibit immune activation, they often have off-target effects, leading to inflammation of various immune-mediated organs or tissues.
can sometimes be severe, especially when both anti-CTLA-4 and anti-PD-1 are used, resulting in up to 60% of 3-5 adverse events.
, although rare, occurs when serious medically-sourced events occur.
this new range of adverse events requires rapid and effective communication between oncologists and various organ specialists and physicians to optimize the management of various immuno-related adverse events.
hope of a cure belongs to only a few patients, and one of the greatest successes of ICI is that, despite the interruption of treatment, long-term remission can be achieved, bringing great hope for the cure of some patients.
in melanoma patients who have reached full remission, this means that all visible metastasis is completely gone.
is now generally accepted that treatment can be discontinued after at least six months of treatment for such patients, as it is estimated that the risk of recurrence is less than 10 per cent in the current five-year follow-up.
in the ICI era, such a long period of complete relief was completely unthinkable.
, however, not all types of cancers respond like melanoma, so data on the likelihood of discontinuation of treatment for other cancers are premature.
patients are usually quite positive about cancer immunotherapy.
are usually in favor of the idea of fighting cancer by mobilizing their immune systems.
because of this frequent attachment to treatment strategies, patients are likely to be more actively involved in treatment and, at least at the beginning of treatment, interaction between patients and doctors can be facilitated.
counterproductive effect is that immunotherapy is to some extent a victim of its success.
The appeal of this treatment strategy to patients and the general public, coupled with the simplification and modification of media coverage, has set very high expectations and has deeply disappointed ICI treatment for patients who have not been able to meet their commitments, and they remain the majority.
it took a long time for end-of-life immunotherapy to become part of an active circle of cancer drugs.
the past decade, ICI has developed and licensed for multiple cancer types at an unprecedented rate.
, despite the tremendous progress, ICI has not completely solved the problem of cancer treatment.
with immune checkpoint immunotherapy, a door to cancer treatment has opened, but the number of cases will not decrease.
hope for the next decade is to predict biomarkers of ICI efficacy and toxicity, as well as pharmacoetic parameters for optimizing ICI programmes and new combinations.
: Robert, C. A decade of immune-checkpointors in cancer therapy. Nat Commun 11, 3801 (2020). Source: Translational Medicine Network, !-- content display ends -- !-- whether the login ends.