Ask AI
Back Back
Immunotherapy in Solid Tumor

CE / CME

Improving Outcomes With Immune Checkpoint Inhibitors for Solid Tumors

Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit

Pharmacists: 0.50 contact hour (0.05 CEUs)

Physicians: maximum of 0.50 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 0.50 Nursing contact hour

Released: June 18, 2026

Expiration: December 17, 2026

Patrick Forde
Patrick Forde, MD, PhD
CME/CE Information

Activity

Progress
1 2 3
Course Completed

PD-1/PD-L1 Mechanism of Action

First, we begin with the rationale and mechanism of action for using PD-1/PD-L1–based immunotherapy in patients with solid tumors. Next we highlight some of the latest clinical trial data and most recent FDA approvals, including the use of SC formulations for commonly used ICIs in clinic.

Anti–PD-1 antibodies, such as pembrolizumab or nivolumab, bind PD-1 receptor on the surface of T-cells, which promotes T-cell activation and targeting of tumor cells. By contrast, PD-L1 antibodies, such as durvalumab or atezolizumab, work by binding the PD-L1 receptor on the surface of tumor cells or immune cells, which leads to its downregulation in tumor cells and increased activity or activation of T-cells.1

Under deregulated conditions, overexpression of PD-1 and PD-L1 receptors leads to dampening of autoimmunity, which allows cancer cells to remain undetected and escape the immune system. Under noncancer–related circumstances, such as in autoimmunity, upregulation of these receptors may partially protect people from conditions like colitis, inflammatory bowel disease, and myocarditis. However, cancer cells will co-opt this mechanism, coat themselves in PD-L1, and therefore protect themselves from our own T-cells, which should be eliminating cancer cells in our body.

Download

CTLA-4 Mechanism of Action

Anti–CTLA-4 antibodies such as ipilimumab or tremelimumab block CTLA-4 signaling primarily during early T-cell priming in the draining lymph node rather than predominantly within the tumor microenvironment.1 By inhibiting this negative regulatory pathway, these antibodies enhance antitumor T-cell activation and expansion, which can promote subsequent trafficking of activated T-cells into the tumor. In this way, CTLA-4 blockade may complement PD-1 or PD-L1 inhibition, as seen in some settings such as melanoma, NSCLC, and renal cell carcinoma.2-4

Unlike PD-1 or PD-L1 inhibitors, which act more directly at the level of the tumor microenvironment, CTLA-4 antibodies work earlier in the cancer–immunity cycle by strengthening the initial immune response. This distinct mechanism helps explain why CTLA-4 and PD-1 pathway inhibitors may have cooperative clinical activity when used together.

Download

Approved ICI Therapies

Across multiple solid tumors, there have been several ICIs approved for targeting of PD-1, PD-L1, and CTLA-4.5-17 However,  we focus this discussion on the most commonly used ones. 

More recently, we have also seen the introduction of the LAG-3 ICI, which binds to the LAG-3 receptor on activated T-cells, blocking its interaction with ligands such as MHC class II and FGL-1. In addition, we have the combination of nivolumab anti–PD-1 with relatlimab, which blocks LAG-3.18,19

Download

Rationale for Combining ICI With Chemotherapy

Combining chemotherapy with immunotherapy is generally done in settings where chemotherapy is already an active therapy, for example, in small-cell lung cancer, advanced skin cancer (melanoma), and renal cell carcinoma.20-22

There are 2 very different mechanisms suggesting the synergy between the 2 treatment modalities: (1) chemotherapy directly kills cancer cells, causing tumor cell lysis and potential release of neoantigens from those lysed tumor cells, which can stimulate antitumor immunity, and (2) addition of immunotherapy deepens and prolongs response to cancer therapy.23,24

Download

Recent Approval of ICI Products in SC Formulation

A recent development in the last 24 months was the approval of SC formulations for atezolizumab with hyaluronidase, nivolumab with hyaluronidase, and pembrolizumab with berahyaluronidase alfa.25-27

This is a remarkable advancement after approximately 10-15 years of using intravenous (IV) immunotherapy options across various solid tumors. Now we have access to SC formulations, which represent an advancement with potential for saving time and resources in the clinic setting.

Download

Carmen is being considered for chemoimmunotherapy after shared decision-making and now needs counseling about AEs that should prompt contact with the care team.

As you educate your patient about identifying potential AEs with immunotherapy for treatment of her cancer, which of the following should you tell her may be a common AE experienced by patients receiving chemoimmunotherapy and should be reported to you for assessment and management?

BACK | NEXT