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T-Cell Fitness and Myeloma

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T-cell fitness is critical for myeloma survivors. And, according to the article linked below, continual myeloma treatments can exhaust t-cells. So what’s a MM survivor to do?

Considering that multiple myeloma is an incurable blood cancer, the FDA therapy plan for all newly diagnosed MM patients is to undergo toxic therapy after toxic therapy until the MM patient runs out of options-

confronting either-

  • T-cell exhaustion and life-threatening infections
  • Multi-drug resistance and MM overwhelming the patient

How can myeloma patients enhance the fitness of their T-cells?

Here are several approaches that can be considered to enhance T-cell fitness in myeloma patients:

1. Exercise

  • Moderate exercise has been shown to improve immune function, including T-cell activity, in cancer patients. Regular, gentle exercise can increase circulation, enhance immune surveillance, and reduce inflammation.
    • Low-impact exercises like walking, yoga, swimming, or cycling can be beneficial.
    • However, the level of physical activity should be tailored to the patient’s overall condition and energy levels.

2. Nutrition

  • A nutrient-dense diet rich in antioxidants, vitamins, and minerals supports immune function.
    • Vitamin C, D, E, zinc, and selenium play essential roles in supporting T-cell activity.
    • Foods rich in omega-3 fatty acids, like fatty fish, flaxseeds, and walnuts, help reduce inflammation and enhance immune health.
    • Probiotics and prebiotics (e.g., fermented foods like yogurt, sauerkraut) support gut health, which is closely tied to immune system function.
  • Proper hydration is also essential to keep cells, including T-cells, functioning well.

3. Immunotherapy and T-cell Activating Therapies

  • Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide, commonly used in treating multiple myeloma, have been found to stimulate T-cell activity and boost the immune system.
    • IMiDs can enhance T-cell activation, proliferation, and anti-tumor activity.
  • CAR-T cell therapy involves modifying a patient’s T-cells to better recognize and attack myeloma cells, though maintaining T-cell fitness is crucial for the success of this therapy.

4. Targeted Treatments to Improve T-cell Function

  • Checkpoint inhibitors, such as drugs targeting PD-1/PD-L1 or CTLA-4, help “unleash” T-cells by blocking the inhibitory signals that tumors use to evade immune attack. These inhibitors can help reinvigorate exhausted T-cells.
  • Clinical trials are exploring other ways to enhance T-cell fitness, such as T-cell agonists that directly stimulate T-cell function.

5. Reducing Immunosuppressive Factors

  • Reducing tumor burden with chemotherapy or targeted therapies can lessen the immunosuppressive environment that myeloma creates. Myeloma cells often produce factors that suppress T-cell activity, and reducing the number of these cells can allow T-cells to function more effectively.
  • Minimizing use of corticosteroids where possible, since they can dampen the immune response, may also be important in optimizing T-cell fitness.

6. Vaccination and Infections Prevention

  • Vaccination against preventable infections (e.g., flu, pneumonia) is important for myeloma patients, as infections can further weaken T-cell function and the immune system. Preventing infections helps the body focus its immune resources on cancer-fighting efforts.
  • Prophylactic treatments against common infections like herpes zoster or fungal infections can prevent infections that may otherwise tax the immune system.

7. Sleep and Stress Management

  • Adequate sleep is essential for proper immune function, including T-cell health. Sleep deprivation can impair T-cell activation and immune response.
  • Stress management techniques (e.g., meditation, mindfulness, deep breathing exercises) can reduce chronic stress, which is known to suppress immune function.

8. Nutritional Supplements (With Medical Guidance)

  • L-glutamine supplementation may improve T-cell function and reduce chemotherapy-induced immunosuppression, but should be used under medical guidance.
  • Curcumin, found in turmeric, has shown potential immune-boosting effects in some studies, although further research is needed in the context of multiple myeloma.
  • Vitamin D supplementation (if deficient) can support immune function, including T-cell responses.

Sadly, the therapies listed above cited to boost T-cell fitness are largely evidence-based non-conventional therapies. Meaning, none of these therapies is FDA approved and probable not be prescribed by the patient’s oncologist.

If you would like to learn more about non-conventional MM therapies email me a question or a comment at David.PeopleBeatingCancer@gmail.com

Thank you,

David Emerson


Impacting T-cell fitness in multiple myeloma: potential roles for selinexor and XPO1 inhibitors

“Competent T-cells with sufficient levels of fitness combat cancer formation and progression. In multiple myeloma (MM), T-cell exhaustion is caused by several factors including tumor burden, constant immune activation due to chronic disease, age, nutritional status, and certain MM treatments such as alkylating agents and proteasome inhibitors.

Many currently used therapies, including:

  • bispecific T-cell engagers,
  • anti-CD38 antibodies,
  • proteasome inhibitors,
  • and CART-cells,

directly or indirectly depend on the anti-cancer activity of T-cells.

Reduced T-cell fitness not only diminishes immune defenses, increasing patient susceptibility to opportunistic infections, but can impact effectiveness MM therapy effectiveness, bringing into focus sequencing strategies that could modulate T-cell fitness and potentially optimize overall benefit and clinical outcomes…

Additional clinical studies are needed to understand how T-cell fitness is impacted by diseases and therapeutic factors in MM, to potentially facilitate the optimal use of available treatments that depend on, and impact, T-cell function. This review summarizes the importance of T-cell fitness and the potential to optimize treatment using T-cell engaging therapies with a focus on XPO1 inhibitors.,,

The importance of T-cell fitness

In the context of CAR-T therapy for hematological malignancies, T-cell fitness is the ability of a T-cell to generate an immune response that mediates the elimination of malignant cells and provides durable protection from relapse ().

T-cell exhaustion is defined by poor effector function, and characterized by reduced T-cell proliferation, increased expression of inhibitory receptors such as checkpoint inhibitors, and a distinct transcriptional signature (, ).

In MM, disease progression is also associated with an altered T-cell repertoire including a reduction in bone marrow and peripheral blood effector T-cells, leading to an overall decrease in T-cell fitness ()…

T-cell exhaustion has been a crucial limiting factor in hematologic malignancy studies utilizing autologous CAR-T therapy (, , )…

T-cell fitness can be negatively affected by multiple factors, including prior treatments, increased age, malnutrition, and systemic inflammation (Figure 1)…

In bispecific antibody therapies, given that most of these agents have been developed with continuous therapy schedules, accumulating data also point to the relevance of treatment-free intervals in functional and transcriptional rejuvenation of T cells ()…

Summary and future directions

CAR-T therapy and bispecific antibodies show promise in the treatment of hematologic malignancies, but efficacy is likely dependent on the status of a patient’s immune system, tumor microenvironment, and prior treatment history (, , ). T-cell exhaustion, driven by age, disease burden, and prior cancer treatment, is a critical limiting factor of these therapies ()…

 

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