Aging-associated immune system changes in multiple myeloma: The dark side of the moon.
Bibliographic record
Abstract
Multiple myeloma (MM) is a disease of the elderly. Changes that occur in the immune system with aging, also known as immunosenescence, have been associated with decreased tumor immunosurveillance and are thought to contribute to the development of MM and other cancers in the elderly. Once MM establishes itself in the bone marrow, immunosenescence related changes have been observed in the immune tumor microenvironment (iTME) and are driven by the malignant cells. The efficacy of novel immunotherapies used to treat MM has been blunted by detrimental iTME changes that occur at later disease stages and are, to some extent, driven by prior therapies. In this review, we discuss general changes that occur in the immune system with aging as well as our current knowledge of immunosenescence in MM. We discuss the differences and overlap between T cell senescence and exhaustion as well as potential methods to prevent or reverse immunosenescence. We focus predominantly on T cell immunosenescence which has been better evaluated in this disease and is more pertinent to novel MM immunotherapies. Our lack of understanding of the drivers of immunosenescence at each stage of the disease, from precursor stages to heavily pretreated MM, represents a major barrier to improving the efficacy of novel and existing therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".